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Mission Statement
Outreach & Education. What is the brain made of? What do different parts do? How do we study it? And why should my tax money pay for brain research? These are all questions I have heard from my friends and family, and answering some of these questions is the primary goal of Interstellate. I hope Interstellate provides some insight into how the brain works, what it is made of, how we study it, and why it is important. While Interstellate is first debuting in the neuroscience community, the goal is to reach our broader communities and include a diverse range of scientific fields! Celebration. Science is not easy and the publication of research projects can take years! The secondary goal of Interstellate is to celebrate all of the components of scientific research - from the images generated from breakthrough findings to the experiment that didn't quite go right. Interstellate provides a platform for all neuroscience images to be seen and celebrated. Inspiration. After a hard day at the bench, beautiful brain images motivate and inspire me. I hope that Interstellate can provide inspiration to the scientific community by showing neuroscience research through several different lenses and showcasing how our colleagues are tackling science questions. I also hope that Interstellate provides a glimpse into what it is like to be a neuroscientist in hopes of recruiting the next generation of science explorers. Art. At the very least, Interstellate is a collection of breathtaking images contributed by outstanding scientists that can be appreciated by all science curious individuals. Participation & Profit. Participation in Interstellate Volume 1 and Volume 2 is on a volunteer basis. All images were donated for outreach and educational purposes, with permission from the parties involved. Interstellate does not generate profit from Volume 1 and Volume 2. Hard copies are sold at printing and shipping costs. Any markup helps support shipping copies to contributors across the globe. Science for everyone, everywhere. Starting in 2018, Interstellate will be expanding beyond neuroscience and will begin to include several scientific fields. To contribute please visit: http://interstellate.com/submission. Please read the following page for more information regarding our exciting future. About the Cover. Neuroimaging is a non-invasive way to examine the human brain. To investigate memory mechanisms in the hippocampus, high-resolution magnetic resonance imaging can be used to image brain activity and anatomy. Our cover image is made from 40 individual ultra-high resolution 7T MRI scans by David Berron, Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg and German Center for Neurodegenerative Diseases Magdeburg, Germany.
Image Credit: Carlos Aizenman Art
Text
Logo By: Christine Liu
interstellate@gmail.com
www.interstellate.com
Caitlin M. Vander Weele Founder & curator of Interstellate Graduate Student, Tye Lab, MIT Estimated date of PhD: April 13, 2018
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Follow us & get in touch!
@interstellate_
I'm graduating and so is Interstellate! In 2018 Interstellate will be growing up! Interstellate is already officially a business and running it will (finally) be my full-time job following the completion of my PhD. While the neuroscience community has done a trmendous job in contributing and promoting Interstellate, there is so more science out there! While I am still in the process of establishing the logistics, the goal is (and always has been) to create a platform for grassroots science communication. Science research shouldn't be kept behind closed doors, let's share the worlds found underneath our microscopes. How will this change the Interstellate? Much of Interstellate will remain the same — or even get better! I'll still be working to collect and share stunning science images. Contributors will continue to be credited for their hard work whenever their image is used and each image will explain a science fun fact! What will change is the distribution of Interstellate materials. To continue to do this work I need to support myself and that means reissuing Interstellate materials for profit. While Volumes 1 and 2 are non-profit projects, future versions will be priced so that earnings can be invested into the company— meaning I'll get to work on making Interstellate materials and merchandise more polished and accessible! So stay tuned for our online store (neuron dresses, large-format prints, and hardcover books anyone?) and exciting new updates. Importantly, the science community is the backbone of Interstellate, so reach out if you have ideas, thoughts, or concerns for the future of this extraordinary project we have created.
Looking towards The future
Science x Art x Outreach
interstellate
Image Credit: Helen Hou, Sabatini Lab, Harvard Medical School
Interstellate reflects the natural entanglement of science and beauty. Scientists admire the aesthetics of experimental design (“a beautiful experimentâ€), the ensuing observations (“a beautiful resultâ€), and scientific presentation (“a beautiful talkâ€). This manner of speaking does not reflect laziness in adjective choice or an impoverished vocabulary, instead scientists are easily seduced into pondering the aesthetics of what they do as it offers a reprise from their typical, drier pursuits. Even in physics, the acceptance of new theories is hastened by elegant explanatory equations. Beauty is seen in simplicity, such that ratios, dimensionless quantities, and the unexpected emergence of previously defined constants are particularly prized. In some cases, this was to the detriment of the discovery of truth, such as the insistence of Greek astronomers on explaining the movement of the cosmos by action along circles. Aristotle had declared the simple circle the most perfect and beautiful form, and the Ptolemaic constructions of astronomy, based on movement along circles, held throughout Greek, Islamic, and Medieval European cultures despite their failure to explain observation. Toppling these beautiful, albeit baroque and evermore complicated, circle-based models required the emergence of mathematical beauty in the form of Kepler’s law of equal area, Newton’s formula for gravitation force, and eventually Einstein’s theories of relativity. In biology, where mathematical theories do not yet reign, beauty is discovered within the physical world revealed by our dissections, measurements, and observations. Our earliest inspirations come from Vesalius, Willis, Ibn al-Haytham and others who used their remarkable artistic skills to produce striking drawings of the nervous system exposed by their dissections. Early microscopists like Leeuwenhoek and brain explorers like Golgi and Ramon y Cajal also drew by hand what their lenses and chemical techniques revealed. I do not know if the ornate and invariably beautiful cellular and circuit drawings that we still admire today are thus because these early scientists focused on visually appealing parts of the nervous system or if such images have been selectively retained through history.
You are about to experience Volume 2 of Interstellate and celebrate its carefully curated and annotated neurobiology-focused images. Dozens of individuals have submitted their studies-turned-artwork and countless more researchers, students, and non-scientists will enjoy this tome. Before we do, however, it is worth pondering why Interstellate has been such as resounding success, both with neurobiologists and those outside the field.
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Volume 2 Foreword
Reconstructed astrocyte. Image Credit: Jason Pitt & Savio Chan, Northwestern University.
Dendrite and axon labeled in the amygdala by iontophoretic injection of Lucifer Yellow. Image Credit: Tina Gruene & Rebecca Shansky, Northeastern University
In the modern era, there is little need for hand drawings (although let’s not forget the origins of Neurolucida) as first analog, and later digital devices, directly capture and enhance the intricate structures of the nervous system. At the small end, new technologies exposed minuscule sub-cellular structures– fusing and endocytosing vesicles arrested by the original freeze-slam machine of Heuser and Reese and perfected by the flash-and-freeze variant of Watanabe and Jorgensen. Across the thin synaptic cleft, flashing dendritic spines whose activity is reported by 2-photon microscopes descended from the original designs of Denk and Webb. On the other end, organ-focused technologies – Brainbow, Clarity, Tractography – seem expressly designed to produce kaleidoscopic images of circuitry. Gorgeous imagery will continue to be produced by neurobiologists as long as the field exists. I’m particularly looking to two fields for such output. The elegant math and physics behind super-resolution microscopy reveal features of cells and neurons – think of the periodic axonal actin rings exposed by Zhuang’s STORM microscopes and the lamellopodia continuously ruffling under the minimal toxicity of Betzig’s lattice light sheet – never before accessible to light microscopy but their full potential for neurobiological discovery has not yet been realized. Dynamic growth cones, the neurotransm-
Dr. Bernardo Sabatini Principal Investigator Professor of Neurobiology Harvard Medical School https://sabatini.hms.harvard.edu
itter receptor inserting machinery that powers synaptic plasticity, and the nanometer organization of the plasma membrane await their moment in the spot light and their future spreads in Interstellate. Similarly starting to make an impact in neurobiology is the melding of information aesthetics and big data, in which the visualization tricks of the former are applied to the immense and at first visually intractable data sets produced by massive sequencing of individual cells and genomes, simultaneous recordings of activity of thousands of cells, and modeling of neural networks of high depth and complexity. The results of these efforts, once the niche realm of the techies but now represented on Pinterest (https://www.pinterest.com/explore/ data-visualization-techniques/), will transform how we interact with, explore, and present high-dimensional data sets. These may force future volumes of Interstellate to move beyond the static and 2-dimensional realm of the printed page. Enjoy the images that follow. Please feel pride from seeing the presentation of your own work (I certainly do for the images from my lab) and revel in the artistry of others. However, also use these as they were intended – as a medium to explain to non-scientists what motivates scientists, what we hope to discover, and what small steps we have taken towards the grand goals of neurobiology.
Clear mouse brain generated with CLARITY technique where lipids are removed and replaced with transparent hydrogels to allow whole brain imaging. Image Credit: Caitlin Vander Weele, Anna Beyeler, & Kay Tye, MIT.
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Image Credit: Blush, solar etching by Elizabeth Jameson
Table of Contents
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MACRO - Brain, Behavior, & Cognition ................................ pg. 7 1x - Systems & Circuits .............................................................. pg. 21 5x- Gross Neuroanatomy ......................................................... pg. 33 20x - Cells & Signaling ............................................................... pg. 49 100x - Subcellular ....................................................................... pg. 63 MAYDAY! - Neuropsychiatric Disorders ........................... pg. 75 Acknowledgements .................................................................... pg. 88 Writing & Editing Team .............................................................. pg. 89 Contributor Affiliations ............................................................ pg. 90 Sponsors .......................................................................................... pg. 94
Interstellate 3D Lou Beaulieu-Laroche, Harnett Lab, MIT
A selection of this year’s Interstellate images have been prepared to be experienced in Augmented Reality (AR). A 3D version of select images will appear to hover above the page where the image is printed. You will be able to interact with the 3D model with your phone or tablet, and take pictures with the model to share. Aivia 6 was used to create the 3D models featured. More on #Aivia6 at Booth 2924 (SfN17) and www.drvtechnologies.com/aivia6 This image is of two nearby neurons during whole-cell recordings from the soma and distal apical dendrite of layer 5 pyramidal neurons in rat temporal association cortex.
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Storms of electrical activity and tidal waves of chemicals weave the very fabric of our minds. Our brains are made up of over a hundred billion cells, intricately connected and ever pulsating over some quadrillion synapses. This communication is not random or haphazard. It is subtle, yet influential. It is efficient, yet vulnerable. It is what makes up our complex thought processes – a feat of evolution that we are still a long way from fully understanding.
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Perhaps the most transformative discoveries to date were made at the wake of the 20th century by the Spanish anatomist Santiago Ramón y Cajal, the “Father of Modern Neuroscienceâ€, whose work paved the path to systematic investigation of brain structure and function. Motivated by a metacognitive desire to understand what makes us understand, the last seventy years saw the birth and rapid maturation of neuroscience as a field unlike any of its predecessors. Combining knowledge and approaches across physics, chemistry, biology, pharmacology, psychology, computer science, and mathematic, neuroscience surfaced as perhaps the most interdisciplinary science humanity has ever encountered. The Society for Neuroscience was founded in 1969 with a membership that grew steadily to nearly 40,000 in 2014. The enormous popularity of neuroscience as a field is in no small part due to the significance of its mission. After all, what could be more exciting than understanding a thing of such beauty and complexity? The impact of such a feat will transform humanity as we know it. It will empower a new generation of innovative neurotechnology mimicking and augmenting human intelligence. It will transform how we learn and educate by unlocking the formidable potential of the human mind. It will empower scientists and clinicians to eradicate brain diseases and promote brain health. It will have countless legal applications from understanding criminal behavior to novel therapies for drug addiction and abuse. It will impact economic growth and development as we better understand the basis of human decision making. It will elucidate the basis of social relationships and the underpinnings of ethics, morality, and religion. It will open up new dialogues to understand radical and extremist behavior, military conflict, bias, discrimination, and other social phenomena that have shaped our civilization over thousands of years. I am often asked to estimate how much we have uncovered about the brain. While many would estimate our collective knowledge at about 10-15% of what is to be learned, my estimates are an order of magnitude lower. Perhaps the discrepancy is motivated by a desire to keep learning. Neuroscience gives scholars a rare chance to remain perpetual students – never ceasing to surprise us, constantly humbling us, and motivating us to work together to solve humanity’s biggest challenges.
Image Credit: Astra S. Bryant, Stanford University
Dr. Michael Yassa Principal Investigator Director of the Center for the Neurobiology of Learning & Memory University of California, Irvine
A Grand Quest
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Heart & Soul Sam Joshva Baskar Jesudasan, Winship & Todd Labs, University of Alberta
Neuroscience is a field of scientific research aimed at understanding the nervous system – the control center of thought and behavior. The processes by which this occurs span a wide range of components; from molecules on one end, to complex cognition on the other. Imaged here is a primary glial cell culture labeled with GFAP (green) and vimentin (red). GFAP labels astrocytes while vimentin is expressed in both astrocytes and fibroblasts. Nuclei are labeled by DAPI (blue).
In Interstellate Volume 2, we will explore the field of neuroscience by adventuring through the scaling factors by which we study the brain. Shown here is a horizontal view of the corticospinal tract projecting to higher somatosensory and prefrontal brain regions. This image was collected with diffusion spectrum imaging (DSI), a non-invasive technique used to measure macro- and micro-structural changes in white matter.
META TO MICRONS Steven Granger, Yassa Lab University of California, Irvine
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A secondary goal of neuroscience research is to understand brain function in neuropsychiatric disease states, such as addiction, depression, and schizophrenia. Imaged here is a dissociated hippocampal cell expressing a synaptic transmembrane protein. Unfortunately, this cell has undergone stress, resulting in a process known as 'beading' or 'blebbing' of the membrane.
In sickness & Health Austin M. Ramsey, Blanpied Lab, University of Maryland School of Medicine
Every new experiment, like the ones exemplified in these pages, brings us closer to understanding how our brains work, in both health and disease. Our advances will allow us to generate better, more targeted therapies for brain disorders by pinpointing the specific components that have malfunctioned. Imaged is a neurosphere of human glioblastoma cancer cells, the most aggressive type of primary brain tumor.
POTENT POTENTIAL Agnese Solari, Florio Lab, University of Genova, Italy
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Some scientists study how brain activity in humans correlates with various thoughts or behaviors, while others use animal models to establish causal relationships by directly manipulating neuronal signals. On an even finer scale, some research probes the growth, development, and functionality of individual cells. Illuminated here are the protein skeletons of astrocytes (green) and neurons (yellow), both of which were made in a dish from mouse neural stem cells.
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Cultural events Samantha Yammine, van der Kooy Lab, University of Toronto
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Population Statistic Mehdi Jorfi, Massachusetts General Hospital, Harvard Medical School
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A cell is the smallest building block of life and the human brain is composed of a vast network of over 100 billion of them. This network shapes our reality, emotions, and actions. Neuroscience aims to unravel how these cells dictate how we perceive and interact with our environment. This image shows a ball of neurons derived from human stem cells, immunostained for MAP-2 (neuronal cell marker) and nuclei.
Brain cells, called neurons, are dynamic. They communicate with one another by sending electrical or chemical signals in order to transmit information to, from, and within the brain. This image displays pyramidal cells (biocytin, violet) in the CA2 region of the hippocampus. In green, YFP-positive mossy fibers innervate the CA2 region.
Trees of Life Michele Pignatelli, Tonegawa Lab, MIT
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Kinesthesia Astra S. Bryant, Knudsen Lab, Stanford University
Histology is the study of microscopic anatomy and is one approach used to inspect brain architecture. This transverse slice of the chick brain is stained with Nissl, a traditional dye that labels the nuclei within individual cells. This method highlights the distinct 15-layered wheel of the optic tectum (called superior colliculus in mammals). The layers are differentiated because the size, shape, and spacing of the cells within them vary. The development of fluorescent proteins now allows multi-colored labeling with genetic- and projection-defined specificity.
Socialite Teruhiro Okuyama, Tonegawa Lab, MIT
Neuroscientists study brain anatomy mainly in animal models using various specialized techniques. Although some animals have brains small enough to be imaged completely intact, often brains are cut into thin slices and placed onto glass slides for viewing though a microscope. Here, social memory labeled hippocampal neurons (GCaMP6f, green) are visible alongside α-Calbindin (red) neurons.
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The basic architecture of the brain is strikingly similar in early embryonic stages. Through an extended process of cell multiplication, growth, and selective death, brain cells differentiate and migrate to form distinct networks. These similarities allow scientists to use many different animal models to investigate brain function – including birds, rodents, fish, and many more. This is a macro photo of the head and neck of a 2-week-old chick embryo, stained for bone (purple) and cartilage (blue).
Progress in Profile Ben Nelemans, Theo Smit Lab, Amsterdam Medical Center
By any other name Michael F. Wells, Eggan Lab, Broad Institute, Harvard University
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Unraveling the brain is daunting not only because of its size and complexity, but also because of its diversity. The brain contains hundreds (if not thousands!) of specialized components, which can be subdivided into various regions and cell types. Imaged are rapid neural progenitor cells induced from human pluripotent stem cells forming neural rosette structures. DNA in cell nuclei are shown in blue, Nestin (a neural lineage marker) in green, and PAX6 in red.
Researchers use various methods to identify and label different types of cells based on their connectivity, molecular markers, and genetic makeup. By expressing fluorescent proteins or other visual tags within them, they can be individually inspected and analyzed. Here, human neurons (cyan) and astrocytes (red) work together to make a synaptically active cell culture.
Teamwork Elliot Glotfelty, McNutt Lab, United States Army Medical Research Institute of Chemical Defense
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Dr. Shruti Muralidhar Postdoctoral Fellow Susumu Tonegawa Lab Massachusetts Institute of Technology
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Integral Integration
From finding food and mates to avoiding threating situations, the brain is barraged by cues in our environment that need to be quickly and effectively deciphered. The nervous system helps animals survive and thrive by giving them the ability to experience, exploit, and learn from their environments.
Neuronal networks help you experience a lot of things – a hot breeze on a summer’s day at the beach, the taste of warm and soft chocolate cake, and the sound of your mother’s voice. They also help generate appropriate responses to the different sensations you feel – you decide to take a dip in that cool inviting water after all, you pour yourself a glass of cold milk to go with that warm cake, and you smile because you haven’t heard your mothers voice in so long! Studying the myriad of shapes, sizes, and orientations of neurons has been the foundation of neuroscience. Since the 1800s, neuroscientists have marveled at the tortuous and sinewy shapes that they found under their microscopes. Thin slices of brain tissue stained with colloidal silver were the first ever sources of single neuron images. Different parts of the brain yielded many different shapes and sizes of neurons, revealing completely unknown territory. Santiago Ramon y Cajal and Camillo Golgi were two of the fearless pioneers who drew out precise maps of these unchartered brain regions, with keen eyes and patient hands. Today’s neuroscientists still turn to basic histochemistry and anatomy to gather clues about unknown neuronal function and connectivity. Over two centuries of evolving techniques has changed the way researchers look at neurons. Using a variety of methods, the nervous system can now be studied with unprecedented levels of specificity. From extensive features like myelin sheaths all the way down to single groups on ion channels on the neuronal membrane, we can obtain images from any level at any resolution. In true collaborative spirit, neuroanatomy has also immensely benefited from contributions from all corners of science. Physicists have contributed to better microscopes, chemists have discovered better staining techniques and biologists have both discovered and designed new markers that have propelled the field forward. Using all of these technologies, we now have the power to image the smallest dendrite, just a few micrometers across. This series of images shows how information gets passed into and out of the brain – each part of a different system and studied in various model organisms. Despite this diversity, these images truly drive home the awe-inspiring scale and organization of the peripheral and central nervous systems.
Image Credit: Caitlin Vander Weele, MIT
Our nervous system helps us make sense of our world by integrating sensory information from the major senses: touch, smell, vision, taste, and sound. Each sensory signal is captured by a specialized receptor and is transmitted to a designated brain region for further processing. These signals allow us to recontruct and navigate our ever-changing environment. This image is a glancing section of a mouse retina, tagged with three small molecule labels: taurine (red), glutamine (green), and glutamate (blue).
Reconstructing reality Bryan William Jones Lab, University of Utah, Moran Eye Center
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The nervous system is divided into two parts: the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is composed of the brain and the spinal cord, while the PNS consists of nerves that connect the brain with the rest of the body. Imaged are traveling fiber tracts labeled with green fluorescent protein and cell bodies (endoplasmic reticulum, red) in the cerebellar cortex.
Enter the Void Joy Zhou, Sillitoe Lab, Baylor College of Medicine
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The sciatic nerve provides the main connection between the spinal cord and the lower limbs. The nerve is actually a bundle of many small nerve fibers that are each connected to an individual neuron in the spinal cord. These fibers are either "sensory" (peripherin, green) or "motor" (red, ChAT) and are surrounded by myelin (white). Here, the circular nerves are surrounded by muscle tissue (red). DNA in cell nuclei is labeled by DAPI (blue).Â
Tributaries Ewout Groen & Hannah Shorrock, Gillingwater Lab, University of Edinburgh
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Sensory neurons convert external stimuli, like sound or touch, into internal signals which are then processed inside the brain. For example, fruit fly (Drosophila) larva must avoid bright sunlight, where they can dry out and easily be seen by predators. To detect high intensity light and other noxious stimuli the larva has sensory neurons tiling its entire body. These cells can sense when the animal is in danger, send signals to the central nervous system, and cause the larva to move away from danger. Class IV dendritic arborization neurons are labeled in cyan and a subset of epithelial cells in orange.
Light sensitive Fillip Port, Bullock Lab, LMB, Cambridge
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TAIL FLIP Zen Faulkes, University of Texas Rio Grande Valley
Motor neurons originate in the spinal cord and project out into the body where they innervate muscles. Signaling across these connections promotes muscle contraction and motor movement. Shrimp and other crustaceans have a powerful, innate escape response to predators. By forcefully flexing their abdomen, they are able to quickly swim away from potential danger. A population of motor neurons in the abdominal ganglia, shown here by cobalt and nickel staining, control the “fast flexor†muscles that enable these rapid movements.
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SEARING SEA Gregory Corder and Sarah Low, Scherrer Lab, Stanford University
Our body protects itself from catastrophic tissue damage by allowing us to feel pain, a process called nociception. Sensory neurons embedded in our skin sense pain when receptors expressed on their axon terminals are activated. These electrical signals are then relayed to the brain and signal the presence of a noxious stimulus. Pictured are peripheral pain fibers (or nociceptors) expressing mu-opioid receptors (MOR, red) and a light-sensitive channel, Channelrhodopsin-2 (ChR2, green). Neurofilament 200 is shown in blue.
High Beams Jaroslav Icha, Norden Lab, Max Planck Institute of Molecular Cell Biology and Genetics
The eye represents a critical interface between the brain and the external world. It incessantly shifts and moves, often imperceptibly and beyond our control, to acquire information from a rich environment.The retina, a light sensitive layer of cells at the back of the eyeball, translates our visual world into electrical brain signals. Pictured is the retina of a larval zebrafish.
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Some sensory and motor information is relayed directly into the brain, rather than through the spinal cord, via cranial nerves. Nearly one-third of our twelve cranial nerves are dedicated towards vision and eye movement. This depth-coded image depicts the six extraocular muscles of a fish eye, which enable it to move. These six muscles are controlled by the activity of three cranial nerves: oculomotor (III), trochlear (IV), and abducens (VI) nerves.
Direct Connect David Schoppik, Schier Lab, Harvard University
Whether it's your favorite song blaring out of the radio, the laughter of your best friend, or the roar of the crowd at a baseball game, your brain is working together with your ears to process sound. Nucleus laminaris neurons (brown, HRP) detect differences in sound arrival time between the two ears. This enables us to localize a sound, or pinpoint its source.
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Source Code Katie L. Willis, Carr Lab, University of Maryland, College Park
Before our brain tells us where our friend is standing, our ears are transforming the sound of her voice into signals that allow us to distinguish what is being said and who is saying it. This happens in the cochlea. The cochlea is located inside our ears and helps translate sound vibrations into nerve impulses that can be deciphered by our brain. Αlpha-tubulin (red) forms microtubule bundles that support hair cells in the cochlea, which resonate at specific frequencies in response to sound waves moving through fluid in the ear. These movements generate electrical signals that are sent to the brain for further processing.
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Translating Sound Dan Jagger, UCL Ear Institute, University College London
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Kristen P. D'Elia Graduate Student Neuroscience & Physiology New York University School of Medicine
Image Credit: Jeremy Day Lab, University of Alabama at Birmingham
It is easy to demonstrate where we lack knowledge about how the brain functions, but often harder to keep in mind how research has driven us to new understandings beyond previous generations’ wildest dreams. Some concepts neuroscientists today might take for granted, such as how different areas of the brain are involved in specialized functions, were extremely controversial not so long ago.
Building Blocks
The human mind is a marvel. Crafted with just enough precision to allow stereotyped behaviors and abilities between individuals, and with just enough flexibility to make uniqueness a core component of our humanity. The general map of our nervous system is carefully drawn by developmental mechanisms of chemical gradients, signaling pathways, and electrical activity. These cascades are evolutionarily ingrained resulting in all brains having the same basic structure and organization. Importantly, this wiring allows a map of function to be imposed consistently from individual to individual, guiding doctors and scientists alike. This similarity extends between species, permitting neuroscientists to focus their studies on homologous regions in many model organisms such as primates, mice, and zebrafish. Just a few centuries ago, the brain was thought to be a homogenous structure with generalized mental capacity. It was in the 1740s when Emanuel Swedenborg theorized that the cerebral cortex was divided into functionally distinct loci. This notion stemmed from his observations of brain damage where symptoms, such as paralysis or cognitive deficits, varied with lesion position. Localization was not seriously considered until a century later when physicians and scientists, such as Pierre Paul Broca and Gustav Fritsch,were able to provide clinical and experimental evidence. Case studies, in addition to experiments in animals, allowed comprehensive maps of function in the brain to be drafted with compiling data. Functional localization in the brain has empowered neuroscientists to progress rapidly in defining regionalization of our behaviors. Current maps can act as a guide, but there is constant debate over the boundaries drawn. Should this area be expanded? Should a region be divided into multiple? How are multiple functions reflected in overlapping regions? The theory doesn’t even begin to touch plasticity. How do these regions vary between individuals? How does experience shape our maps? How can these maps change after injury? We have come far in our understanding of the many folds of the human cortex and evolutionarily older structures that lie beneath it, but we still have a long way to go. It seems the mosaic that is our nervous system appears more intricately complex and beautiful with each passing year.
The brain in is composed of two hemispheres that are essentially mirror images of one another. The hemispheres are connected by a large bundle of nerve fibers called the corpus callosum. This is a human brain illustrating fiber tracts using diffusion MRI tractography. Each trajectory is colored according to its direction of travel (red: left–right; green: front–back blue: up–down). The corpus callosum is easily identified by the large red bundle located in the middle of the two hemispheres.
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Wiring the brain Alexander Leemans, PROVIDI Lab, University Medical Center Utrecht
One major principle in neuroscience is functional specialization, the idea that different brain regions are specialized to perform distinct functions. For example, a brain region called the olfactory bulb processes our sense of smell. Here, thousands of olfactory neurons in the nasal cavity project into the olfactory bulb. The M71 receptor is tagged with a GFP reporter (green) and dopaminergic neurons (cyan) surround the glomeruli. In the deeper layers, granule cells (yellow) create an inhibitory network and here, they express a designer receptor (DREADD, red).
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Divide & Conquer Jeremy C. McIntyre Lab, University of Florida
Brain blueprint Matthias Prigge, Yizhar Lab, Weizmann Institute of Science
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The brain is composed of a collection of subregions which specialize in various behaviors and cognitive processes. Identified in this parasaggital mouse brain section are regions discussed in the following pages. Here, retrogradely labeled neurons are seen throughout the brain (cyan), as well as their axonal projections to the brainstem and spinal cord. The slice is labeled with an antibody against tyrosine hydroxylase (TH, magenta) which identifies noradrenergic and dopaminergic cells.
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Tailored Tools Guillaume Jacquemet & Emilia Peuhu, Ivaska Lab, University of Turku
The functions of brain subregions were initially investigated by damaging or electrically stimulating a specific site and observing how it changed behavior or thought. Some of the first human subjects had brain damage caused by accidents or cancerous tumors. For example, the famous neuroscience patient HM had damage to the memory center of the brain and was unable to form new memories. The cells in this cancer tumor stably express F-actin tdMars (red) and were stained for DAPI (blue) and Fibronectin (green).
The olfactory bulb is crucial for a proper sense of smell and the first stop for odorant information in the brain. Olfactory neurons located in the mucosa of the nasal cavity provide direct input into the olfactory bulb where chemical odorants are decoded by specialized clusters of neurons called glomeruli. This image shows a section of a transgenic mouse olfactory bulb, where mitral and tufted cells express the calcium reporter GCaMP6 (pseudo-colored red). The section was also immunostained for the muscarinic receptor CHMR3 (green) and counter stained for cell nuclei (DAPI, blue).
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Inhale, exhale Jeremy C. McIntrye Lab, University of Florida
Liking & Wanting Ben Saunders, Janak Lab, Johns Hopkins University
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The ventral tegmental area and the substantia nigra together comprise a brain region called the ventral midbrain. These two structures contain the majority of the brain's dopamine neurons – a chemical signal important for reward and motor movement. This is an image of the rat ventral midbrain showing dopamine cells (TH, white) co-expressing a fluorescent calcium indicator (GCaMP6, green) and a red-shifted excitatory opsin (ChrimsonR, red) for integrated optogenetic manipulation and fiber photometry recordings.
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Dopamine from neurons in the ventral midbrain is released in a brain region called the striatum. The striatum has diverse roles in motor planning, decision making, and behavioral reinforcement. Dysfunction of the striatal dopamine pathway is associated with many neuropsychiatric disorders, including Huntington's disease, Parkinson's disease, bipolar disorder, and addiction. Here, entopeduncular nucleus- (EP, green) and the zona incerta- (red) projecting neurons were accidentally labeled in the dorsal portion of the striatum.
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Logical Locomotion Daniel Knowland, Lim Lab, University of California, San Diego
relay Gil Mandelbaum and Trevor Haynes, Sabatini Lab, Harvard Medical School
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The thalamus is generally thought to be a sensory processing and relay station. With the exception of the olfactory system, sensory information from the external environment is funneled through the thalamus and projected to various regions in the brain. In addition, the thalamus also regulates sleep and consciousness. Damage to the thalamus can cause profound insomnia or even coma. Imaged are retrogradely labeled thalamic neurons which reveal topographic organization of the parafascicular nucleus, a nucleus in the thalamus.
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high society Cody Siciliano & Xinghong Chen, Tye Lab, MIT
Try to remember your last social interaction– Who was it? Was it pleasant? What did you talk about? The prefrontal cortex, situated right behind your forehead, is a processing powerhouse involved in both guiding social experiences when they are happening and also recalling the memory of it. In addition, the prefrontal cortex is engaged during complicated cognitive processes like planning, decision-making, and short-term memory. This image highlights prefrontal pyramidal neurons that are connected to hindbrain-projecting neurons, labeled with rabies tracing.
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Partition Mary Phillips, Pozzo-Miller Lab, University of Alabama at Birmingham
The hippocampus is a highly organized seahorse-shaped structure that is essential for forming new memories. The hippocampus has 3 distinct regions, referred to as cornu ammonis 1-3, or CA1-3. Here the hippocampus has been stained for proteins that surround cells and strengthen their structure to facilitate communication, called perineuronal nets (pink). In the hippocampus, these nets are mainly specific to small inhibitory interneurons, but in the CA2 region perineuronal nets lose interneuron specificity and engulf the CA2 region of the hippocampus resulting in the large pink flare.
Ebb & Flow Shane Hegarty, O'Keeffe & Sullivan Labs, University of Cork, Ireland
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The dorsal raphe nucleus (situated just below the heart-shaped ventricle) contains neurons that produce the neuromodulator serotonin (often abbreviated 5-HT). These neurons have been shown to regulate sleep-wake cycle, mood, and social interaction. Ventricles, like the one pictured here, are cavities within the brain containing cerebrospinal fluid (CSF). CSF cushions the brain and provides chemical stability. This is a midbrain section of a Zeb2 conditional knockout mouse.
Surprise, Surprise Jesse Gammons, Lindsay Schwarz Lab, St. Jude Children's Research Hospital
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Activation of norepinephrine (NE)-containing neurons in a brain region called the locus coeruleus (LC) is important for enhanced arousal in a wide range of situations, such as exploring a new environment or responding to a stressful or painful cue. This image shows LC neurons expressing dopamine-beta-hydroxylase (the enzyme that synthesizes NE, cyan) and neurons that have been recently activated (cFos, magenta).
Mini-Brain Samantha Amat, Jason Christie Lab, Max Planck Florida Institute for Neuroscience
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While the cerebellum is most well studied for its involvement in balance and motor coordination, it is also associated with social behavior, reward learning, among many other processes. In humans, the cerebellum contains around 50 billion neurons (over half of the total neuronal population) and receives diverse input from many brain regions, thus making it a main neural processing area, or "mini-brain". Pictured are climbing fiber axons (green) projecting from the inferior olive to the cerebellar cortex and targeting Purkinje cells (red).
At a Crossroads Louis-Etienne Lorenzo, Y. De Koninck Lab, CERVO Brain Center, Laval University
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In order for us to feel sensations and interact with our environment, the brain requires extensive feedback from the body. Nerves – carrying information about pain, temperature, touch, vibration, and position – travel from the skin and enter the spinal cord, where they interact with other neurons in the dorsal horn (pictured here). These neurons then ascend, carrying rich information about the environment to the brain. This image displays inhibitory neurons (glutamic acid decarboxylase, red) and activated astrocytes (glial fibrillary acidic protein, green), along with stress-related proteins (heat shock protein 27, blue) in the spinal cord of a mouse.
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Since the beginning of modern neuroscience, scientists have tried to visualize neurons under a microscope. Initially, they struggled to see individual cells – the first neuron stains dyed every neuron they touched, and since they are packed so tightly, a scientist could not decipher one neuron from the next. But in 1873, Emilius Golgi created a stain that revolutionized how we could view the brain. His stain only dyed a selection of neurons, which allowed scientists to see single neurons and interpret their unique morphological properties. Golg's revealed the neuron’s unusual structure. Like other cells, each neuron has a cell body, or soma, where the cell’s housekeeping proteins reside. But that's where a neuron's similarities to other cell types end. Out from the top of a neuronal soma sprouts branched projections called dendrites, and out the bottom, a wire-like structure, called the axon, extends away from the cell. Like how rain falls on the leaves on a tree, electrochemical signals land on dendrites. Through a series of events, this signal initiates an electrical pulse, or action potential, that travels through the dendrites, across the soma, and down the axon, eventually to the axonal terminal, where it connects with another neuron or group of neurons through synapses. Typically, a neuron does not communicate with a single neuron on either end; in fact, most neurons receive signals from and project their own signals to thousands of other neurons, propagating a constellation of activity that mediates and coordinates the complex events that define our thoughts and behavior. As you will see in the coming pages, we’ve come a long way from the Golgi stain, as advances in our ability to visualize neurons has drastically changed how we look at the brain. Today’s microscopy techniques make it possible to translate this intricate architecture into beautiful works of art. It has also advanced our understanding of brain connectivity and communication. In 10x, we will explore the stunning structure of brain cells and how they interact with one another to give rise to who we are.
Connecting the dots
Your brain contains a dense mesh of tens of billions of neurons, along with a roughly equal number of glia, connected in an unimaginably complex network that governs how you think, feel, and move. Everything you do; how you respond to events and objects in our environment, make decisions, and behave, is mediated by electrical signals passed along this network from one cell to another.
Image Credit: Victoria Forster, Newcastle University
Dr. Ben Marcus CG Life www.scrireach.org
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Neurons transmit signals preferentially in one direction, from dendrites towards axons. The cell body, also called the soma is the circular structure (pink) containing the cell's DNA (blue) and integrates the signals received from other neurons at its dendrites. To transmit information to other parts of the brain, the cell sends a long projection, called the axon, to release a chemical signal there. Observed here using a spinning-disk microscope is one such discrete unit—a rat hippocampal neuron imaged in all its singular beauty, along with elaborate branches of dendrites and axons (actin, green; DAPI, blue; MAP2, purple).
Cornerstones Guillaume Jacquemet, Ivaska Lab, University of Turku
axon
dendrites
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cell body
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Arborization Daniel Bloodgood, Kash Lab, University of North Carolina
Dendrites are thin projections from the cell that receive excitatory and inhibitory chemical signals from other neurons, and convey them as electrical impulses. These impulses then combine at the cell body where they determine whether or not the cell will fire an action potential. In some cells, the dendritic arbor can be quite intricate such as in pyramidal neurons in the cortex shown here. These highly branched processes allow the cells to fine-tune their firing by sampling the activity of thousands of neurons.Â
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Close Contact Annie Liu, Nathaniel Urban Lab, University of Pittsburgh
The connection point between two neurons occurs at a synapse. To transmit information between neurons, the upstream neuron (termed the pre-synaptic cell) releases chemical signals onto its receiving neuron (termed the post-synaptic cell) Here, a glomerulus (green) synapses onto its post-synaptic targets (red), These structures form a glomerular module, the basic odor-coding unit of the olfactory bulb.
Neurotransmitters are the chemical messengers of the nervous system. They are passed across the synapses of adjacent neurons, either exciting or inhibiting the synaptic pathway, The two most prevalent neurotransmitters found in neurons are glutamate and GABA (Gamma-Aminobutyric Acid); however over a 100 different neurotransmitters have been identified. These cells from the eye imaginal disk of a fruit fly (Drosophila) are labeled with neural and glial markers to allow various cell types and pathways of transmission to be visualized.
courier Bruno Vellutini Zuzana Vavrusova, Vanessa Knutson Marine Biological Lab Woods Hole
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Impulse Control Michael Derr, BioSciences Division, ThermoFisher Scientific
Electrical signals propagate along neurons (known as action potentials) and trigger the release of chemical neurotransmitters onto adjacent neurons. In these cortical neurons, the green labeling indicates synapsins, the gatekeepers of neurotransmitter release. They are anchored to the cell skeleton (red) and become tagged when an action potential arrives. Upon tagging, they allow the fusion of vesicles containing neurotransmitter with the cell membrane, causing the chemical to be released and act on the next neuron.
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Receiving End Gregory Corder, Scherrer Lab, Stanford University
Neurotransmitters influence the activity of their post-synaptic partners by binding to receptors located in their cell membranes. Similar to a lock and key, when neurotransmitter attachs to a receptor, a pore opens causing the neuron to be activated or inhibited – depending on the type of neurotransmitter and its respective receptor. Pictured are cells expressing mu-opioid receptors (MOR, red) and a light-sensitive protein (ChR2, green). 

Glutamate is the most abundant neurotransmitter in the brain and accounts for over ninety percent of synaptic connections. Glutamate provides a "go" signal by causing neurons on which it acts upon to become depolarized, or a shift in electrical charge where the cell become less negatively charged. If enough excitatory input is received and the neuron becomes sufficiently depolarized, the cell will fire an action potential and propagate its own signal down its axon. This image of a rat brain was created by soaking the brain in a heavy metal called osmium. The osmium binds the outside of cells (those that use glutamate and others) and allows us to see deep within the brain with x-rays.
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Pronto Javier Alejandro Masis, David Cox Lab, Harvard
Manduca Sexta Kristyn Lizbinski, Dacks Lab, West Virginia University
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The primary inhibitory, or "stop" signal in the brain is the neurotransmitter GABA. GABA causes cells to become hyperpolarized, or more negatively charged and less like to fire an action potential. This image shows a section of a moth's antennal lobe, analgous to the olfactory bulb. The large cluster of GABA-containing interneurons (yellow) and their extensions work together with serotonin (cyan) across spherical structures called glomeruli (magenta).
In contrast to the fast synaptic transmission by GABA and glutamate, there are several neuromodulators that have slower post-synaptic effects. The most abundent neuromodulators are dopamine, norepinephrine, serotonin, and acetylcholine. Dopamine mainly works through modulating the activity of neurons expressing either dopamine type-1 (D1) or dopamine type-2 receptors (D2). Shown here is an image of forebrain dopamine type-1 receptor neurons expressing Kaede in a larval zebrafish. These neurons are located in the subpallium, the putative location of the zebrafish striatal homologue. The image is color-coded for depth.
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Changing the gain Nicholas Guilbeault, Thiele Lab, University of Toronto - Scarborough
The brain is the most energy- and oxygen-consuming organ in the body. Just like the other organs, the brain needs blood to function properly. Blood courses through the blood vessels of the nervous system delivering oxygen and retrieving waste. Here a whole mount mouse retina is stained with a plant lectin that labels endothelial cells of the retina's vasculature.
Streamlined Crystal L. Lantz, Quinlan Lab , University of Maryland - College Park
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While neurons are the main signaling cells in the brain, glia are the other major class of cells in the brain. Glia, derived from the Greek word for "glue", physically support neurons and help maintain a healthy internal environment within the brain. Moreover, glial cells are increasingly recognized as key regulators of synaptic communication between neurons. Imaged is a mixed rat primary glial culture labeled with GFAP (green) and vimentin (red), GFAP labels astrocytes, a major subtype of glia, and vimentin labels astrocytes and fibroblasts.
PARTNER IN CRIME Sam Joshva Baskar Jesudasan Winship & Todd Labs, University of Alberta
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This is an image of radial glia in the leopard gecko forebrain (GFAP, cyan). Radial glia are a type of neural stem cell that produce neurons, which then migrate down their lengthy processes. In mammals radial glia are present during development but not adulthood. In many non-mammalian species capable of brain regeneration, including lizards, radial glia are retained throughout life.
eublepharis Rebecca McDonald, Vickaryous Lab, University of Guelph
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The nervous system is simultaneously the most highly-organized and diversely populated organ system we have, and neurons must assume a wide range of both highly specific and divergent roles. Subtle changes at the molecular level attune these neurons to their surroundings, their information flow, and their history.
James R. Howe VI Graduate Student Neurosciences University of California, San Diego
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So far, we’ve journeyed through most of the brain’s strata, moving through the furrows of the cortex, along projections down to the limbic subnuclei, and into their underlying microcircuits. However, these are all composed of even more intricate architectures: the spectacular elements within the neurons themselves. Take a look at a synapse on an earlier page: it is not only a contact between those two neurons, but it holds an array of vesicles zipping into a membrane in concert, opposite a finely-tuned balance of receptors bound to a dense lattice right below the surface. Such organization is not exclusive to the synapse, but instead supports every structure in the nervous system. Just as all these higher, complex structures are composed of lower, simple structures, the mind’s emergent phenomena arise out of molecular phenomena. After all, appreciating art and learning to talk are simply, at the most basic level, very specific ways that salt moves through pores in our neurons. If we want to fully comprehend why some songs remind us of past summers, or why a child’s first word was ‘cat,’ we must understand the molecular basis behind these experiences. If we want to fully comprehend why some babies are born unable to hear, or why some autistic children will never learn to speak, we must know the molecular basis behind these disorders. For these reasons (among many more), the relevance of subcellular processes can hardly be overstated. Join us in this section as we descend deeper, into the neuron. Here, we can watch neural stem cells differentiate into mature neurons, growth factors making their dendritic arbors sprout and bloom. In more mature cells, we can see webs of actin crisscrossing the cytoplasm or leading creeping growth cones as they traverse. All of the following images underscore the intrinsic beauty of some of the finest structures within our nervous system.
Image Credit: Daniel Knowland, University of California, San Diego
super Resolution
networking Victoria Forster, van Delft Lab, Newcastle University
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Cells from the central nervous system (CNS) can be grown in a dish – a preparation called in vitro. This image shows glial progenitor cells that have been sparsely plated – as they grow, they start to form network connections with each other as the basis for the development and growth of full neurons or glial cells.
Stem cells are undifferentiated cells-- meaning they have not yet transformed into a specific type of cell (e.g., neuron, glia, etc.). Once isolated from the embryonic or adult brain, stem cells can be grown in a petri dish where they assemble into spherical clusters called neurospheres. Neurospheres are composed of the small initial group of stem cells, as well as a diverse population of neurons and glia that they have created. In the neurosphere pictured here, thin processes of newly-made neurons (βIII-tubulin, red) emerge from a tightly packed cluster of cell bodies (bisbenzamide, blue).
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Planetary Suzanne Crotty & Louise Collins, Nolan Lab, University College Cork, Ireland
While seemingly simple in structure, the lining of the cell, known as the cell membrane, is more than just a wall separating the inner cellular space with the outer environment. Rather, the cell membrane retains countless receptors, channels, transporters, and enzymes that tightly regulate the ions and proteins that control cell activity. This cell contains a calcium-sensitive dye (Oregon Green), displaying the degree of calcium stored inside.
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Holding cell Wilson Adams, Mahadevan-Jansen Lab, Vanderbilt University
Inside neurons are numerous pockets filled with neurotranmitters, called vesicles. When a cell becomes sufficiently depolarized and fires an action potential, these vesicles dock on the inner surface of the cell membrane and release their contents into the synapse. Imaged are primary rat hippocampal neurons which have become interconnected by neurofilament tracts (green). Labeled in blue are the nuclei of neurons and in red, proteins that associate with the neurofilaments.
Chemical capsules Elliot Glotfelty, McNutt Lab, United States Army Medical Research Institute of Chemical Defense
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Support System Lorna Young, Higgs Lab, Dartmouth College
The cytoskeleton is an essential part of the cell. Similar to the skeleton of our own bodies, the cytoskeleton provides the cell with structure and movement abilities. The image shows a human bone osteosarcoma epithelial cell (U2OS) stained for actin and focal adhesion proteins. Signaling between adhesions and the cytoskeleton allows the cell to adapt to the changing cellular environment. 

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MOVERS & SHAKERS Christophe Leterrier, NeuroCyto Lab, CNRS-Aix Marseille University
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Components of the cytoskeleton, like the protein actin help neurons move and find appropriate synaptic partners. Actin forms a structure called microfilaments, which have a tough but flexible framework. By elongating and contracting microfilaments, cell mobility and division are enabled. In this image, young rat hippocampal neurons in culture are labeled for actin (orange) and microtubules (blue), another part of the cytoskeleton.

In FLUX Simon Chamberland, Tóth Lab, Université Laval
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When a cell fires an action potential, calcium rushes into the cell through pores located in the cell membrane. This influx of calcium is necessary for the docking of vesicles and the release of neuotransmitter into the synapse. Pictured is a network of hippocampal neurons expressing GCaMP, a calcium sensor that causes neurons to transiently illuminate when high levels of calcium are detected (i.e., when the cell is active). Warmer colors indicate the neurons that were more actively firing during this acquisition of this image.
Deoxyribonucleic Acid (DNA) is the foundational code for life. DNA provides the instructions for the manufacturing of the proteins cells require. Every cell of an organism contains the same DNA code, but depending on the cell type, only selective parts of the code will be used, giving rise to different cells types. DNA is packed tightly inside the cell nucleus. In this image of a monkey kidney cell, the DNA of the cell can be seen as the blue circle entangled in actin, microtubules, clathrin-coated pits.
Élan vital Christophe Leterrier, NeuroCyto Lab, CNRS-Aix Marseille University
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Countless combinations of genes make nearby cells distinct from one another. A gene is a functional unit of DNA that codes for a specific protein and is the hereditary unit that is passed from parents to children. Here, the brain of the fruit fly, Drosophila melanogaster, was engineered to express Brainbow transgenes under the control of one such gene. This technique labels neurons with random assortments of fluorescent proteins so they can be differentiated from each other during subsequent analysis. Ultimately, researchers hope that Brainbow technology will reveal subtle differences between neurons based on their expression of a particular gene.
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technicolor transgenes Tim Mosca Lab, Thomas Jefferson University
While a cell’s DNA provides a list of genes that are present, additional mechanisms dictate which genes are active and which are not. This level of gene control, termed epigenetics, can command the type of proteins that are made, ultimately influencing what a cell becomes. In cultured mouse neurospheres seen here, epigenetics modifications can be used to reliably differentiate stem cells and generate neurons (βIII-tubulin), astrocytes (GFAP), and oligodendrocytes (O4).
fine tuning Ilan Vonderwalde, Morshead Lab, University of Toronto
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While some treatments are available, their efficacy is limited. In order to develop novel treatments with higher efficacy for these disorders, a better understanding of the neural mechanisms underlying these illnesses is required. Moreover, stigma and discrimination prevent most individuals with a mental illness from seeking help and treatment. Increased understanding of these disorders will not only help uncover novel treatment avenues, but also begin to diffuse the stigma surrounding mental illness, thereby allowing for better care for affected individuals and their families. Modern neuroscience uses a variety of methods to study the mechanisms underlying these disorders, ranging from clinical investigations using genetic, neuroimaging and electrophysiological methods to pre-clinical investigations using stem cells as well as in vivo, ex vivo and in vitro methods. Neuroimaging studies provide a window into the human brain and allow for the assessment of the contribution of genetic variation or disease states on the function of the brain, and can provide valuable information related to the brain structural or functional correlates, as well as the neurotransmitter release. Moreover, the ability to assess behaviors during these imaging studies facilitates the study of temporal dynamics of brain function and how they might contribute to behavior or psychopathology. Pre-clinical studies, on the other hand, allow for a greater ability for the causal manipulation of brain circuitry through cutting-edge optogenetic and chemogenetic tools. With the ability to reverse-translate findings from genome-wide association studies and create transgenic animals (either lacking expression or expressing genetic variations), these studies allow neuroscientists to assess the role of genes in normal and pathological brain function, which can provide novel druggable targets. Moreover, dissecting brain circuitry underlying psychopathology can pave the way for the development of neuromodulation-based treatment methods (e.g., deep brain stimulation, transcranial magnetic stimulation) targeting specific brain regions implicated in the disorders.
Found in Translation
According to the World Health Organization, one in four people in the world will be affected by mental illness (e.g., depression, anxiety, substance use, psychosis) at some point in their lives with around 450 million people currently suffering from such conditions. This makes psychiatric illnesses one of the leading causes of disability worldwide.
Image Credit: Joseph Zaki, Harvard University
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Dr. Jibran Khokhar Assistant Professor Department of Biomedical Sciences University of Guelph, Ontario, Canada
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Despite the prevalence of neuropsychiatric disorders, methods for treating them are remarkably limited. Pharmacotherapies, or therapeutic drugs, are often ineffective and accompanied by serious, unintended side effects. Of course this is not surprising considering drugs wash over the entire brain and have effects on systems that may not be the cause of the disease state. Primary neuroscience research aims to understand how components of the brain work in healthy states, so that we may develop better, more specific treatments for neuropsychiatric diseases. This image depicts tractography streamlines from the human cortex to the striatum. Lighter blue colors indicate greater diffusion signal magnitude in voxels traversed by streamlines.
Dissecting disease Kevin Jarbo, Verstynen / Cognitive Axon Lab, Carnegie Mellon University
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Numerous neuropsychiatric disorders are related to neural circuit dysfunctions that can be modeled in non-human animals. Model organisms allow researchers to directly test the mechanisms underlying the proposed effects of pharmacotherapies. In this image, neurons in the mediodorsal thalamus that directly project to the prefrontal cortex were made to express a chemogenetic receptor (hM3Dq, green) that allows for selective activation of this pathway. Activation of these thalamic projections alone are capable of mimicking the typical effects of antidepressants, suggesting that increasing thalamic activity has potential therapeutic value.
Imitation Games Oliver H. Miller, Hall Lab, Hoffman-La Roche
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Anxiety is a long-lasting state brought about by internal or external factors. While generally adaptive, chronic anxiety, like in post-traumatic stress disorder, can be highly detrimental. To identify brain regions implicated in anxiety, like the ventral hippocampus (pink), neurons can be tagged with fluorescent proteins (blue) during a state of high anxiety. This label can last for the lifetime of the mouse to facilitate circuit-based understandings of neuropsychiatric disorders.
City of Stars Jalina Graham, Wiltgen Lab, UC Davis
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BAd HaBITS Morgan Zipperly, Day Lab, University of Alabama at Birmingham
When something feels good, we want to keep doing it. For some people, this desire is overwhelming and may develop into addiction. Addiction is the compulsive engagement in a rewarding behavior, such as drug use, despite the presence of negative consequences (e.g., health, finances, personal relationships, etc.). Dopamine release within the nucleus accumbens, a subregion of the striatum, plays a crucial role in the development of addiction. In this image, neurons in the nucleus accumbens were transduced with a virus to express a light-sensitive channel (ChR2, green) and cell nuclei were strained in blue.
The nervous system develops from an orchestrated series of gene regulation, chemical signaling, cell proliferation, and programmed cell death. Not surprisingly, mistakes early in this elaborate routine can have a profound impact on the adult organism. In the fruit fly (Drosophila), the eye imaginal disc gives rise to the adult eye. Here, an overexpressed protein (rhodopsin, red) during a crucial phase in development caused a degenerated, abnormal adult eye (ER stress, green). Using this fly model, the effects of genetic variation on retinal development can provide insight into retinal degeneration in humans.
Under Construction Rebecca Palu & Clement Chow, Chow Lab, University of Utah
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Depression is a mood disorder characterized by a persistent feeling of sadness and a loss of interest in activities we usually find enjoyable. While there is no single neural underpinning that causes depression, serotonin certainly plays a role. Serotonin is a neurotransmitter that affects mood and anxiety. In depression, serotonin levels are abnormally low and as such, common antidepressants (selective serotonin reuptake inhibitors [SSRIs]) work by increasing the length of time that serotonin stays in the synapse. This image shows neurons that have a receptor for serotonin in the fruit fly (Drosophila) brain (cyan & yellow).
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Mood swings Tyler Sizemore, Dacks Lab, West Virginia University
Spectral Adam Tyson, Andreae Lab, King's College London
Autism is a congenital developmental disorder with symptoms spanning a large spectrum of severity. Autism is characterized by delayed development in communication, difficulty in social interactions, and highly repetitive behaviors. While autism is a complex condition, involving many genes and environmental factors, abnormalities in the cortical function have been implicated. In this image, cortical cell bodies and axons are being inspected to assess tissue microstructure. This section of tissue was taken from a mouse model of autsim and optically cleared (CLARITY).
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Forget-me-Not Joseph Zaki, Ramirez Lab, Harvard
Alzheimer's Disease is a debilitating neurodegenerative disorder, defined most by profound memory loss. Recent memories are hard to retain, and as the disease progresses, older memories also fade away. The hippocampus is known as the seat of memories in the brain, and is one of the first areas to be affected in Alzheimer's Disease. Here, cells that were active during the acquisition of a fear memory were labeled in the mouse hippocampus (cfos driven ChR2-eYFP).
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HALLUCINATING Caitlin M. Vander Weele, Tye Lab, MIT
Schizophrenia is associated with several cognitive deficits, most notably the inability to understand what is real. Individuals with schizophrenia often have distorted and paranoid perceptions of their worlds, often reporting that they hear voices or that "someone" is after them. While the cause of schizophrenia is still unclear, evidence suggests that the dysregulation of dopamine in the prefrontal cortex an underlying component of the pathology. Imgaged are prefrontal cortex neurons expressing the dopamine type-1 receptor (D1, green) and striatal-projecting neurons (red).
Dopamine release disinhibits outputs of the striatum to initiate movement. However in Parkinson's Disease, the dopamine input neurons to this region die off and patients have problems with motor coordination. The reason for this selective cell death is not well understood, and treatment options are limited. Here we see axon fiber bundles coursing through the striatum.
Disinhibition Daniel Bloodgood, Kash Lab, University of North Carolina
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Forward Thinking Wendy Wang, Lefebvre Lab, University of Toronto
Scientific discoveries often happen when we least expect it. The serendipity through which this occurs brought the world florescent proteins, gene editing, and countless other accelerations towards disease therapies. If the past is any indicator for the future, the beauty of science lies in the unexpected. In the pursuit of knowledge will come quantum leaps in clinical therapies and applications. In the meantime, let us enjoy the by-products of these pursuits: the beautiful images that are Interstellate. Imaged are various neuron types in the cerebellum: molecular layer interneurons (orange), Purkinje cells (green), and cell nuclei (cyan).
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Image Credit: Gwendolyn Calhoon, MIT
Acknowledgements
Dr. David Berron Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg and German Center for Neurodegenerative Diseases Magdeburg, Germany Postdoctoral Fellow and Volume 2 cover image contributor Pasquale D'Silva Thinko Interactive Design Studio Animator & software designer. Interstellate technology & web consultant Dr. Benjamin Saunders University of Minnesota Assistant Professor & creative mind behind the title "Interstellate" Christine Liu UC Berkeley Graduate student, artist, & skilled hands responsible for our logo www.twophotonart.com
Christine Arasaratnam PhD Student, Faull Lab Centre for Brain Research The University of Auckland Auckland, New Zealand Aadil Bharwani MD-PhD Student, The Brain-Body Institute Dept. of Pathology & Molecular Medicine Michael G. DeGroote School of Medicine McMaster University, ON, CA Kristen P. D'Elia PhD Student, Schoppik & Dasen Labs Neuroscience & Physiology New York University School of Medicine, NY, USA Janette Edson Sequencing Manager Queensland Brain Institute The University of Queensland St Lucia, Brisbane, QLD, Australia Kurt Fraser Graduate Student, Janak Lab Department of Psychological & Brain Sciences The Johns Hopkins University, MD, USA James R. Howe VI Graduate Student Neurosciences University of California, San Diego, CA, USA Timal S. Kannangara Postdoctoral Fellow Diane Lagace & Jean-Claude Béïque Laboratories Dept. of Cellular and Molecular Medicine University of Ottawa, ON, Canada Jibran Khokhar, PhD Assistant Professor Department of Biomedical Sciences University of Guelph, ON, Canada
Writing & Editing Team
Image Credit: Anna Beyeler, MIT
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Christopher J. Langmead Head, Servier Drug Discovery Program, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia Ben Marcus, PhD CG Life www.scireach.org Shruti Muralidhar, PhD Postdoctoral Fellow, Tonegawa Lab Picower Institute for Learning & Memory Massachusetts Institute of Technology, MA, USA Tabitha Moses MD/PhD Student Department of Psychiatry and Behavioral Sciences School of Medicine Wayne State University, MI, USA Bernardo Sabatini, PhD Professor of Neurobiology, Principal Investigator Harvard Medical School Harvard University, MA, USA Caitlin M. Vander Weele Graduate Student, Kay Tye Lab Dept. of Brain and Cognitive Sciences Picower Institute for Learning & Memory Massachusetts Institute of Technology, MA, USA Wendy Wang Graduate Student, Julie Lefebvre Lab Dept. of Molecular Genetics University of Toronto / SickKids ON, Canada Michael Yassa, PhD Associate Professor, Director, Principal Investigator Center for the Neurobiology of Learning & Memory University of California, Irvine, CA, USA
Wilson R. Adams Graduate Research Assistant, Mahadevan-Jansen Lab Dept. of Biomedical Engineering Vanderbilt University, TN, USA Carlos Aizenman, PhD Professor, Principal Investigator Dept. of Neuroscience Brown University, RI, USA Samantha Amat Researcher, Jason Christie Lab Max Planck Florida Institute for Neuroscience, FL, USA Jason Askvig, PhD Assistant Professor, Principal Investgator Dept. of Biology Concordia College, MN, USA Lou Beaulieu-Laroche Graduate Student, Mark Harnett Lab McGovern Institute for Brain Research Dept. of Brain and Cognitive Sciences Massachusetts Institute of Technology, MA, USA David Berron, PhD Postdoctoral Fellow Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke-University Magdeburg and German Center for Neurodegenerative Diseases Magdeburg, Germany Anna Beyeler, PhD Assistant Professor, Principal Investigator University of Bordeaux, France Daniel Bloodgood Graduate Student, Kash Lab UNC Neuroscience Curriculum The University of North Carolina-Chapel Hill, NC, USA Astra S. Bryant, PhD Postdoctoral Fellow, Hallem Lab Microbiology, Immunology, and Molecular Genetics University of California, Los Angeles, CA, USA Gwendolyn Calhoon, PhD Postdoctoral Fellow, Tye Lab Picower Institute for Learning & Memory Massachusetts Institute of Technology, MA, USA Simon Chamberland Graduate Student, Toth Lab Dept. of Neuroscience and Psychiatry, CERVO Universite Laval, QC, Canada C. Savio Chan, PhD Assistant Professor, Principal Investigator Department of Physiology Northwestern Univeristy, IL, USA
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Xinghong Chen Visiting Student, Kay Tye Lab Picower Institute for Learning and Memory Massachusetts Institute of Technology, MA, USA Clement Chow, PhD Assistant Professor, Principal Investigator Dept. of Human Genetics University of Utah School of Medicine, UT, USA Gregory Corder, PhD Postdoctoral Fellow, Scherrer Lab Dept. of Anesthesiology, Perioperative and Pain Medicine, Neurosciences Institute Stanford University, CA, USA Jeremy Day, PhD Assistant Professor, Principal Investigator Dept. of Neurobiology University of Alabama at Birmingham, AL, USA Michael Derr, PhD Scientist III, Cell Biology, BioSciences Division ThermoFisher Scientific Trinley Dorje Art Healthcare profressional & anatomical artist https://tdorjeart.myportfolio.com/ Toronto, ON, Canada Zen Faulkes, PhD Professor, Principal Investigator Dept. of Biology University of Texas Rio Grande Valley, TX, USA Victoria Forster, PhD Postdoctoral Fellow, Tabori Lab The Hospital for Sick Children University of Toronto, ON, Canada Jesse Gammons Graduate Student, Lindsay Schwarz Lab Dept. of Developmental Neurobiology St. Jude's Children's Research Hospital, TN, US Elliot Glotfelty Research Assistant, McNutt Lab Neuroscience branch United States Army Medical Research Institute of Chemical Defense, MD, USA Ewout Groen, PhD Postdoctoral Fellow, Gillingwater Lab Centre for Integrative Physiology University of Edinburgh, Scotland Jalina Graham Graduate Student, Wiltgen Lab Neuroscience Graduate Group UC Davis, CA, USA
Contributor Affiliations
Steven Granger Graduate Student, Yassa Lab Center for the Neurobiology of Learning & Memory University of California, Irvine, CA, USA Tina Gruene, PhD Researcher, Shansky Lab Dept. of Psychology Northeastern University, MA, USA Nicholas Guilbeault Graduate Student, Tod Thiele Lab Dept. of Cell and Systems Biology University of Toronto, ON, Canada Trevor Haynes Research Assistant, Sabatini Lab Harvard Medical School Harvard University, MA, USA Shane Hegarty, PhD Research Fellow, Zhigang He Lab Dept. of Neurology Boston Children's Hospital Harvard Medical School, MA, USA Helen Hou, PhD Postdoctoral Fellow, Sawtell Lab Columbia University, NY, USA Jaroslav Icha Graduate Student, Norden Lab Max Planck Institute of Molecular Cell Biology and Genetics Dresden, Germany Dan Jagger, PhD UCL Ear Institute University of College London, UK Elizabeth Jameson Fine Art Artist www.jamesonfineart.com Kevin Jarbo Graduate Student, Verstynen / CoAx Lab Dept. of Psychology & Center for the Neural Basis of Cognition, Carnegie Mellon University, PA, USA Bryan William Jones, PhD Associate Professor, Principal Investigator Joneslab, Moran Eye Center University of Utah, UT, USA Guillaume Jacquemet, PhD Research Associate, Ivaska Lab Turku Centre for Biotechnology University of Turku, Finland
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Sam Joshva Baskar Jesudasan Graduate Student, Winship & Todd Lab Neurochemical Research Unit Department of Psychiatry University of Alberta, AB, Canada Mehdi Jorfi, PhD Research Fellow Center for Engineering in Medicine Massachusetts General Hospital (MGH) Harvard Medical School, MA, USA Daniel Knowland Graduate Student, Byungkook Lim Lab Dept. of Neurosciences University of California, San Diego, CA, USA Vanessa Knutson Graduate Student, Giribet Lab Dept. of Oganismic & Evolutionary Biology Harvard University, MA, USA Crystal L. Lantz, PhD Research Associate, Quinlan Lab Dept. of Biology University of Maryland - Collge Park, MD, USA Alexander Leemans, PhD Associate Professor, Principal Investigator PROVIDI Lab, Image Sciences Institute University Medical Center Utrecht, Netherlands Christophe Leterrier, PhD Team Leader, NeuroCyto Lab NICN Instiute CNRS-Aix Marseille University, Marseille, France
 Kristyn Lizbinski Graduate Student, Dacks Lab Dept. of Biology West Virginia University, WV, USA Annie Liu, PhD MD/PhD Candidate University of Pittsburgh School of Medicine, PA, USA Louis-Etienne Lorenzo, PhD Research Associate, Y. De Koninck Lab Neuroscience Research Laboratory CERVO Brain Center Laval University, QC, Canada Sarah Low Researcher, Scherrer Lab Neurosciences Institute Stanford University, CA, USA Gil Mandelbaum Graduate Student, Sabatini Lab Harvard Medical School Harvard University, MA, USA
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Javier Alejandro Masis Graduate Student, Cox Lab Dept. of Molecular & Cellular Biology Harvard University, MA, USA Rebecca McDonald Graduate Student, Vickaryous Lab Dept. of Biomedical Sciences University of Guelph, ON, Canada Jeremy C. McIntyre, PhD Assistant Professor, Principal Investigator Dept. of Neuroscience University of Florida, FL, USA Oliver H. Miller Postdoctoral Fellow, Knight Lab Dept. of Physiology UCSF, CA, USA Timothy J. Mosca, PhD Assistant Professor, Principal Investigator Dept. of Neuroscience Thomas Jefferson University, PA USA Yvonne Nolan, PhD Senior Lecturer, Principal Investogator Dept. of Anatomy & Neuroscience University of Cork, Cork, Ireland Ben Nelemans Graduate Student, Theo Smit Lab Spinogenesis Group Amsterdam Amsterdam Medical Center, Netherlands Gerard O'Keeffe, PhD Senior Lecturer, Principal Investigator Dept. of Anatomy and Neuroscience University of Cork, Cork, Ireland Teruhiro Okuyama, PhD Postdoctoral Fellow, Tonegawa Lab Picower Institute for Learning & Memory Massachusetts Institute of Technology, MA, USA Jason Pitt, PhD Postdoctoral Fellow Department of Physiology Northwestern Univeristy, IL, USA Rebecca Palu, PhD Postdoctoral Fellow, Chow Lab Department of Human Genetics University of Utah School of Medicine, UT, USA Emilia Peuhu Researcher, Ivaska Lab Turku Centre for Biotechnology University of Turku, Finland
Mary Phillips Graduate Student, Pozzo-Miller Lab Dept. of Neurobiology University of Alabama at Birmingham, AL, USA Michele Pignatelli, PhD Research Associate, Tonegawa Lab Picower Institute for Learning and Memory Massachusetts Institute of Technology, MA, USA Fillip Port, PhD German Cancer Research Center Heidelberg, Germany Matthias Prigge, PhD Senior Intern, Yizhar Lab Dept. of Neurobiology Weizmann Institute of Science, Israel Austin Ramsey Graduate Student, Blanpied Lab Dept. of Physiology University of Maryland, MD, USA Benjamin Saunders, PhD Assistant Professor, Principal Investigator Dept. of Neuroscience University of Minnesota, MN, USA David Schoppik, PhD Assistant Professor, Principal Investigator Department of Neuroscience & Physiology New York School of Medicine, NY, USA Lindsay Schwarz, PhD Assistant Professor, Principal Investigator Dept. of Developmental Neurobiology St. Jude's Children's Research Hospital, TN, USA Rebecca Shansky, PhD Assistant Professor, Principal Investigator Dept. of Psychology Northeastern University, MA, USA Hannah Shorrock Graduate Student, Gillingwater Lab Centre for Integrative Physiology University of Edinburgh, Scotland Cod5y Siciliano, PhD Postdoctoral Fellow, Kay Tye Lab Picower Institute for Learning and Memory Massachusetts Institute of Technology, MA, USA Dana Simmons Graduate Student, Hansel Lab Dept. of Neurobiology The University of Chicago, IL, USA www.dana-simmons.com
Tyler Sizemore Graduate Student, Dacks Lab Dept. of Biology West Virginia University, WV, USA Agnese Solari Graduate Student, Florio Lab Section of Pharmacology Dept. of Internal Medicine University of Genova, Italy Aideen Sullivan Professor Dept. of Anatomy & Neuroscience University of Cork, Cork, Ireland Christos Suriano Graduate Student, Bodznick Lab Dept. of Biology Wesleyan University, CT, USA Adam Tyson Graduate Student, Institute of Psychiatry, Psychology & Neuroscience King’s College London, London, UK Caitlin Vander Weele Graduate Student, Kay Tye Lab Dept. of Brain and Cognitive Sciences Picower Institute for Learning and Memory Massachusetts Institute of Technology, MA, USA Zuzana Vavrusova Graduate Student, Schneider Lab Dept. of Orthopaedic Surgery University of California, San Francisco, CA, USA Bruno Vellutini Postdoctoral Fellow, Tomancak Group Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Ilan Vonderwald Graduate Student, Morshead Lab Institute of Biomaterials and Biomedical Engineering University of Toronto, ON, Canada Michael F. Wells, PhD Postdoctoral Fellow, Eggan Lab Broad Institute Harvard University, MA, USA Katie L. Willis, PhD Research Fellow Dept. of Biology University of Oklahoma, OK, USA
Ian Winship, PhD Associate Professor, Principal Investigator Neurochemical Research Unit Department of Psychiatry University of Alberta, AB, Canada Wendy Wang Graduate Student, Julie Lefebvre Lab Dept. of Molecular Genetics University of Toronto / SickKids ON, Canada Samantha Yammine Graduate Student, van der Kooy Lab Dept. of Molecular Genetics University of Toronto, ON, Canada Lorna Young, PhD Postdoctoral Fellow, Higgs Lab Biochemistry Department Geisel Medical School at Dartmouth, NH, USA Joy Zhou Research Assistant, Silltoe Lab Baylor College of Medicine, TX, USA Morgan Zipperly MSTP Student, Day Lab Dept. of Neurobiology University of Alabama at Birmingham, AL, USA Joseph Zaki Research Assistant, Ramierz Lab Center for Brain Science Harvard University, MA, USA
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Society for Neuroscience 2017 Sponsors List
@thermofisher
Platinum Sponsor
www.thermofisher.com
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Thermo Fisher Scientific Inc. is the world leader in serving science, with revenues of more than $20 billion and approximately 65,000 employees globally. Our mission is to enable our customers to make the world healthier, cleaner and safer. We help our customers accelerate life sciences research, solve complex analytical challenges, improve patient diagnostics, deliver medicines to market and increase laboratory productivity. Through our premier brands – Thermo Scientific, Applied Biosystems, Invitrogen, Fisher Scientific and Unity Lab Services – we offer an unmatched combination of innovative technologies, purchasing convenience and comprehensive services.
@Inscopix
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The Canadian Association for Neuroscience
The Picower Institute for Learning and Memory is an independent research entity within MIT's School of Science. Picower’s diverse array of brain scientists are dedicated to unraveling the mechanisms that drive the quintessentially human capacities to remember and learn, as well as to explore related functions like perception, attention, and consciousness.
@CAN_ACN
https://www.inscopix.com/
The leader in miniature microscopy for circuit neuroscience in freely-behaving animals, Inscopix accelerates breakthroughs in brain science by empowering researchers with a complete solution from biological reagents and cutting-edge instrumentation to powerful data analytics and world-class scientific support.
The Picower Institue for Learning & Memory
http://can-acn.org
GOLD SponsoRS
@MIT_Picower
The Canadian Associaton for Neuroscience (CAN) represents neuroscientists in Canada who are dedicated to advancing brain research. Our association is composed of approximately one thousand researchers, who work at academic instutions across the country. We share the common goal of ensuring neuroscience remains one of the greatest research and innovation strengths of Canada.
Society for Neuroscience 2017
https://picower.mit.edu/
Inscopix
Doric Lenses
www.doriclenses.com
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https://neurophotonics.ca/canadian-neurophotonics-platform
Silver Sponsor
@Neurophotonics
@DRVisionTech
The Canadian Neurophotonics Platform
A global brand of neurophotonics hardware that sets standards for modulated light sources, fiber-optic rotary joints, cannulas or brain implants, miniaturized fluorescence microscopes and fiber photometry systems. With our devices it is possible to visualize and quantify neuronal activity of freely moving animals.
The Canadian Neurophotonics Platform is a technology platform that drives development and maximizes exploitation of leading-edge photonics technologies for the study, diagnostics and treatment of brain diseases. The platform is funded by the Canadian Brain Research Fund through Brain Canada.
