Killam Seminar Series: Human-Specific Modifiers of Cortical Circuits Evolution
Gr芒ce 脿 la g茅n茅rosit茅 des fiducies Killam, Le Neuro convoque lors d鈥檜ne s茅rie de s茅minaires des conf茅renciers d鈥檈xception dont les travaux passionnent ses chercheurs et ceux de l鈥橴niversit茅 麻豆AV.听
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Franck Polleux
Professeur de neurosciences, Universit茅 de Columbia
贬么迟别:听eric.shoubridge [at] mcgill.ca (Eric Shoubridge )
Abstract:听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.
