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SUMMARY:Human-specific genetic modifiers underlying cortical circuit evolu
 tion - Professor Franck Polleux (Columbia University)
DTSTART;VALUE=DATE-TIME:20250925T110000
DTEND;VALUE=DATE-TIME:20250925T120000
UID:https://talks.ox.ac.uk/talks/id/d41d3f0a-5900-4ab8-b706-ebc38c4caa3e/
DESCRIPTION:Two of the most striking features distinguishing human cortica
 l pyramidal neurons (CPNs) from other mammals which are thought to play a 
 role in the emergence of our unique cognitive abilities are: (1) human CPN
 s receive significantly more excitatory and inhibitory synapses than any o
 ther mammalian species including non-human primates and (2) synaptic devel
 opment is strikingly neotenic in humans\, taking years to reach maturation
  compared to weeks or months in other mammalian species. Our lab identifie
 d two human-specific gene duplications called SRGAP2B/C which\, by inhibit
 ing all known functions of the ancestral postsynaptic protein SRGAP2A\, le
 ads to slower (neotenic) rates of excitatory (E) and inhibitory (I) synapt
 ic maturation and increased E and I synapse number (Charrier et al. Cell 2
 012\; Fossatti et al Neuron 2016). We demonstrated that induction of expre
 ssion of human-specific genes SRGAP2B/C in mouse CPNs increases specifical
 ly the number of cortico-cortical synaptic connections they receive leadin
 g to changes in the coding properties of these neurons in vivo as well as 
 improved behavioral performance in a sensory discrimination task (Schmidt 
 et al. Nature 2021). I will also present recent evidence demonstrating the
  function of human-specific SRGAP2B/C in human neurons as key mediators of
  synaptic neoteny\, using a novel xenotransplantation model\, in collabora
 tion with Pierre Vanderhaeghen’s lab (Libé-Philippot et al. Neuron 2024
 ). These results also provide the first evidence that human-specific genes
  such as SRGAP2B/C are not only relevant to understand human brain evoluti
 on but also constitute human-specific disease modifiers. \nI will also pre
 sent new results demonstrating that human-specific SRGAP2B/C genes also ac
 t as master regulators of the timing of structural and functional maturati
 on of microglial cells using both humanized mouse models and SRGAP2B/C los
 s-of-function approaches using human iPSC-derived microglia xenotransplant
 ation in mouse neonatal cortex. Our results demonstrate that SRGAP2B/C-dep
 endent induction of neotenic maturation of microglial cells participates n
 on-cell autonomously to the delayed timing of synaptic maturation in corti
 cal pyramidal neurons. Our results reveal that\, during human brain evolut
 ion\, human-specific genes SRGAP2B/C coordinated the emergence of neotenic
  features of synaptic development by acting as genetic modifiers in both n
 eurons and microglia.\n\nSPEAKER BIOGRAPHY\n\nSince 2013\, Franck Polleux 
 is a Professor of Neuroscience at Columbia University and a Principal Inve
 stigator at the Zuckerman Mind Brain Behavior Institute in New York. He ob
 tained his PhD in 1997 at Université Claude Bernard in Lyon France under 
 the supervision of Henry Kennedy and Colette Dehay. He then did his postdo
 ctoral training with Anirvan Ghosh at Johns Hopkins University. From 2002-
 2010\, he started his independent research career at UNC-Chapel Hill\, the
 n moved to Scripps Research Institute in La Jolla\, CA. \nThroughout his s
 cientific career spanning three decades\, Dr Polleux has focused on the id
 entification of novel cellular and molecular mechanisms underlying the dev
 elopment and function of synapses\, neurons and circuits in the mammalian 
 neocortex. More recently\, his lab started studying the genetic basis of h
 uman brain evolution by focusing on the role of human-specific gene duplic
 ations as genetic modifiers of synaptic connectivity\, circuit function an
 d their impact on cognition. His work demonstrates that human-specific gen
 es such as SRGAP2B/C not only represent human-specific modifiers of brain 
 development but also represent unique human-specific disease modifiers in 
 the context of neurodevelopmental disorders such as autism spectrum disord
 ers. In collaboration with the lab of Attila Losonczy\, he recently starte
 d to study the synaptic and molecular basis of feature selectivity of plac
 e cell emergence using mouse CA1 hippocampal pyramidal neurons as a model.
 \nFor his numerous scientific contributions\, he was awarded several prest
 igious awards such as the Albert L. Lehninger Research Prize for postdocto
 ral research\, the 2005 NARSAD Young Investigator Award\, the 2015 Foundat
 ion Roger De Spoelberch Prize\, a 2021 Nomis Foundation Award and the 2021
  R35 Research Program Award\, a career award from the NIH-National Institu
 te of Neurological Disorders and Stroke (NINDS).\nSpeakers:\nProfessor Fra
 nck Polleux (Columbia University)
LOCATION:Sherrington Library (Sherrington Building)\, off Parks Road OX1 3
 PT
TZID:Europe/London
URL:https://talks.ox.ac.uk/talks/id/d41d3f0a-5900-4ab8-b706-ebc38c4caa3e/
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DESCRIPTION:Talk:Human-specific genetic modifiers underlying cortical circ
 uit evolution - Professor Franck Polleux (Columbia University)
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