Killam Seminar Series: Think Positively: Novel Mechanisms of Modulating Synaptic Plasticity and Implications for Brain Disease
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 McGill.听
Pour assister en personne,听
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Kevin Beier
Professeur associ茅, D茅partement de physiologie et de biophysique, 脡cole de m茅decine, Universit茅 de Californie, Irvine.
贬么迟别:听wayne.sossin [at] mcgill.ca (Wayne Sossin)
Abstract:听Administration of the Zeta Inhibitory Peptide (ZIP) interferes with memory maintenance and long-term potentiation (LTP). However, mice lacking its putative target, the protein kinase PKM2, exhibit normal learning and memory as well as LTP, making ZIP鈥檚 mechanism unclear. Here, we show that ZIP disrupts LTP by removing surface AMPA receptors through its cationic charge alone. This effect requires endophilin A2 (endoA2)-mediated endocytosis and is fully blocked by drugs suppressing macropinocytosis. ZIP and other cationic peptides selectively remove newly inserted AMPAR nanoclusters, providing a mechanism by which these peptides erase memories without altering basal synaptic function. When delivered in vivo, cationic peptides modulate memories on local and brain-wide scales and prevent memory loss in a model of traumatic brain injury. Our findings uncover a previously unknown synaptic mechanism by which memories are maintained or lost.
