Killam Seminar Series: Human-Specific Modifiers Cortical Circuits Evolution

Professor of Neuroscience, Columbia University

Human-Specific Modifiers of Cortical Circuits Evolution

Abstract: Two of the most striking distinguishing features of human cortical pyramidal neurons (CPNs) are: (1) human CPNs receive significantly more excitatory and inhibitory synapses than any other mammalian species including non-human primates and (2) synaptic development is strikingly neotenic in humans, taking years to reach maturation compared to weeks or months in other mammalian species. Our lab identified two human-specific gene duplications called SRGAP2B/C which, by inhibiting all known functions of the post-synaptic ancestral protein SRGAP2A, leads to slower (neotenic) rates of excitatory (E) and inhibitory (I) synaptic maturation and increased E and I synapse number. We also demonstrated that this increased density of E synapses in layer 2/3 cortical pyramidal neurons (CPNs) originates from increased cortico-cortical connections, leading to changes in the coding properties of these neurons in vivo and improved behavioral performance in a sensory discrimination task in mice humanized for SRGAP2C expression. I will summarize recent results demonstrating (1) the function of human-specific genes SRGAP2B/C as critical modifiers of synaptic development in human neurons using xenotransplantation and (2) that SRGAP2B/C also act as human-specific disease modifiers in the context of neurodevelopmental disorders.

Bio: Franck Polleux did his undergraduate and graduate studies at Université Claude Bernard in Lyon, (France) where he obtained his Ph.D. in Neuroscience in 1997. He then joined the laboratory of Anirvan Ghosh at Johns Hopkins University for his post-doctoral training. In 2002, Polleux was hired as an Assistant Professor in the Neuroscience Center and Department of Pharmacology at the University of North Carolina- Chapel Hill. In August 2010, he joined The Scripps Research Institute in La Jolla, California. In November 2013, he was recruited as a Professor in the Department of Neuroscience at Columbia University to join the new Mortimer B. Zuckerman Mind, Brain, Behavior Institute. Throughout his career, Polleux has focused on the identification of the molecular mechanisms underlying the development, evolution and maintenance of neuronal connectivity in the mammalian brain. Specifically, his lab has pioneered the study of the genetic, cellular and molecular basis of human brain evolution.

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