Neuronal Connectivity in Brain Function and Disease: Novel Mechanisms and Therapeutic Targets

Organizers

Thomas F. Franke, MD, PhD

NYU School of Medicine

Dr. Franke is an Associate Professor of Psychiatry, and Biochemistry & Molecular Pharmacology at the NYU School of Medicine. He joined the NYUSoM faculty in 2007. Dr. Franke received his MD in 1992 from the University of Lübeck in Germany and his MD, PhD in Medical Virology in 1995 from Justus Liebig University in Germany. Dr. Franke is a pioneer in the field of Akt signal transduction, in which he was the first to demonstrate the regulation of Akt by growth factors downstream of activated PI 3-kinase. His current work investigates Akt's relevance in behavioral neuroscience by exploring the biochemical and structural consequences of Akt activity in higher-order neural functions. Building on his previous research on the contribution of Akt dysfunction to cancer biology, Dr. Franke employs pharmacology and mutant mouse models to examine Akt's involvement in mental disease, including addiction and depression. His research will expand our current understanding of how Akt contributes to normal brain physiology, and create new opportunities for diagnostic and therapeutic approaches to psychiatric and neurodegenerative disorders.

Eric Nestler, MD, PhD

Icahn School of Medicine at Mount Sinai

Dr. Nestler is the Nash Family Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, where he serves as Chair of the Department of Neuroscience and Director of the Friedman Brain Institute. He received his BA, PhD, and MD degrees, and psychiatry residency training, from Yale University. He served on the Yale faculty from 1987–2000, where he was the Elizabeth Mears and House Jameson Professor of Psychiatry and Neurobiology, and Director of the Division of Molecular Psychiatry. He moved to Dallas in 2000 where he served as the Lou and Ellen McGinley Distinguished Professor and Chair of the Department of Psychiatry at The University of Texas Southwestern Medical Center until moving to New York in 2008. Dr. Nestler is a member of the Institute of Medicine and a Fellow of the American Academy of Arts and Sciences. He is a past President of the American College of Neuropsychopharmacology and President Elect of the Society for Neuroscience. The goal of Dr. Nestler's research is to better understand the molecular mechanisms of addiction and depression based on work in animal models, and to use this information to develop improved treatments of these disorders.

Sonya Dougal, PhD

The New York Academy of Sciences

Caitlin McOmish, PhD

The New York Academy of Sciences

Speakers

Wenbiao Gan, PhD

NYU Langone Medical Center

Dr. Wen-Biao Gan is a professor in the Department of Neuroscience and Physiology and Skirball Institute at New York University School of Medicine. He obtained his PhD in Neurobiology from Columbia University in 1995. Dr. Gan's research focuses on understanding how the brain is able to integrate new information continuously while stably maintaining previously stored memories. Using transcranial two-photon microscopy to study changes in postsynaptic dendritic spines in living mouse cerebral cortex, his laboratory has shown that the majority of dendritic spines in diverse regions of the cortex persist throughout adulthood and can serve as a structural basis for long-term information storage. In addition, learning and novel sensory experience lead to a small degree of new dendritic spine formation via a highly selective process. These new spines likely play an important role in modifying neuronal circuit function and contribute to new information storage. Over the years, his laboratory has contributed to the understanding of how motor learning, fear learning and extinction, stress hormone glucocorticoids, microglia, and sleep affect synaptic plasticity in the living mouse cortex. More recently, his laboratory has developed new behavioral paradigms to image activity of dendrites and dendritic spines in the cortex of awake behaving mice and identified a fundamental role of dendritic calcium spikes in learning-dependent synaptic plasticity.

Bruce McEwen, PhD

Rockefeller University

Bruce S. McEwen obtained his PhD in Cell Biology in 1964 from The Rockefeller University. He is a member of the US National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. He served as President of the Society for Neuroscience in 1997–98. As a neuroscientist and neuroendocrinologist, McEwen studies environmentally-regulated, variable gene expression in brain, mediated by circulating steroid hormones and endogenous neurotransmitters in relation to brain sexual differentiation and the actions of sex and stress hormones on the adult brain, in particular related to structural and functional plasticity via epigenetic mechanisms. His laboratory discovered adrenal steroid receptors in the hippocampus in 1968 that was the gateway for discovering effects of circulating hormones on cognitive function, mood regulation and other CNS functions. His laboratory combines molecular, anatomical, pharmacological, physiological and behavioral methodologies and relates their findings to human clinical information. His current research focuses on stress effects on amygdala and prefrontal cortex, as well as hippocampus, and his laboratory also investigates sex hormone effects and sex differences in these brain regions involved in cognitive function and mood regulation.

Eric Nestler, MD, PhD

Icahn School of Medicine at Mount Sinai

Dr. Nestler is the Nash Family Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai in New York City, where he serves as Chair of the Department of Neuroscience and Director of the Friedman Brain Institute. He received his BA, PhD, and MD degrees, and psychiatry residency training, from Yale University. He served on the Yale faculty from 1987–2000, where he was the Elizabeth Mears and House Jameson Professor of Psychiatry and Neurobiology, and Director of the Division of Molecular Psychiatry. He moved to Dallas in 2000 where he served as the Lou and Ellen McGinley Distinguished Professor and Chair of the Department of Psychiatry at The University of Texas Southwestern Medical Center until moving to New York in 2008. Dr. Nestler is a member of the Institute of Medicine and a Fellow of the American Academy of Arts and Sciences. He is a past President of the American College of Neuropsychopharmacology and President Elect of the Society for Neuroscience. The goal of Dr. Nestler's research is to better understand the molecular mechanisms of addiction and depression based on work in animal models, and to use this information to develop improved treatments of these disorders.

Amy Robinson

MIT

Amy Robinson is the Executive Director of EyeWire, a game to map the brain that began at MIT. EyeWire crowdsources neuroscience, challenging hundreds of thousands of players around the world to solve 3D puzzles, which actually map out neurons. This allows neuroscientists to chart synaptic connections and model circuitry. Robinson has advised The White House OSTP and the US Senate on crowdsourcing and open innovation. Under her leadership, Eyewire's neuroscience visualizations have appeared at TED and in Times Square NYC. She helped create the world's first neuroscience virtual reality experience. Robinson curates the NIH 3D Print Exchange Neuroscience collection, which features several 3D printable neurons discovered by Eyewire gamers. Fast Company credits Robinson with "making neuroscience into a playground for the hot tech du jour." Robinson has written for Vice, the BBC, Nature, and Forbes. She tweets @amyleerobinson. Amy is a long time TEDster and founded the TEDx Music Project, a collection of the best live music from TEDx events around the world. She was named to the Forbes 30 Under 30 in 2015.

Bernardo Sabatini, MD, PhD

Harvard Medical School

Bernardo Sabatini obtained a PhD from the Department of Neurobiology and his MD degree from the Harvard/Massachusetts Institute of Technology Program in Health Sciences and Technology in 1999. Dr. Sabatini chose to not pursue further medical training, and instead began a postdoctoral fellowship in the laboratory of Dr. Karel Svoboda at Cold Spring Harbor Laboratory in New York. After his postdoctoral research, Dr. Sabatini joined the faculty in the Department of Neurobiology at Harvard Medical School in 2001. In 2008 Dr. Sabatini was named an investigator of the Howard Hughes Medical Institute and in 2010 was named the Takeda Professor of Neurobiology at Harvard Medical School. His laboratory seeks to uncover the mechanisms of synapse and circuit plasticity that permit new behaviors to be learned and refined. They are interested in the developmental changes that occur after birth that make learning possible, as well as in the circuit changes that are triggered by the process of learning. Lastly, they examine how perturbations of these processes contribute to human neuropsychiatric disorders such as Tuberous Sclerosis Complex and Parkinson's disease.

In order to conduct their studies, Dr. Sabatini's laboratory creates new optical and chemical methods to be able to observe and manipulate the biochemical signaling associated with synapse function. In 2014 Dr. Sabatini was elected to the American Academy of Arts and Sciences, and was also the recipient of the 2013–2014 A. Clifford Barger Excellence in Mentoring Award. He serves on a number of scientific advisory boards including the Simons Center for the Global Brain, the Max Planck Florida Institute, and others both domestically and abroad. Dr. Sabatini is currently the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS. He lives in Newton with his wife, who is a physician at MGH, and their 3 boys.

David Sulzer, PhD

Columbia University Medical Center

Dr. Sulzer is a Professor of Neurology, Psychiatry, and Pharmacology at Columbia University Medical Center and the New York Psychiatric Institute. He received his Ph.D from the Department of Biology at Columbia University.

Dr. Sulzer's lab (www.sulzerlab.org) is involved in research devoted to understanding the synapses of the basal ganglia, particularly in investigating how synapses of the cortex, striatum, and dopamine neurons are selected to underlie learning and decision making; and elucidating the causes of diseases that produce disorders of the basal ganglia, including Parkinson's Huntington's, drug dependence, autism and schizophrenia. Dr. Sulzer has authored over 150 publications in the field of dopamine and basal ganglia synaptic physiology and disease and has introduced multiple new therapeutic directions.

Relevant approaches explored in the lab include the development of the system for postnatal culture of midbrain dopamine neurons; discovery of co-release of glutamate from dopamine neurons; introduction the mechanism of amphetamine action; the first recording of quantal neurotransmitter release in the CNS, using amperometry at dopamine terminals; discovery of multiple means to alter quantal size, including the effects of L-DOPA, amphetamine, vesicle transporter expression, alpha-synuclein expression, and fusion pore flickering; introduction of the biosynthetic pathway of neuromelanin; introducing the role of macroautophagy and chaperone-mediated autophagy in neurodegenerative diseases; providing the first optical analysis of corticostriatal transmission; invention of fluorescent false neurotransmitters to provide the first optical means to observe neurotransmitter release in brain; identification of the role of glutamate in controlling axonal outgrowth and branching from growth cones; introduction of autophagy as a means to control developmental synaptic pruning in autism and epilepsy; identification of antigen presentation in neuron subtypes in neurodegeneration.