Killam Seminar Series: Think Positively: Novel Mechanisms of Modulating Synaptic Plasticity and Implications for Brain Disease

Supported by the generosity of the Killam Trusts, The Neuro's Killam Seminar Series invites outstanding guest speakers whose research is of interest to the scientific community at The Neuro and McGill University.

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Kevin Beier

Associate Professor, Physiology & Biophysics School of Medicine, University of California, Irvine

Host: wayne.sossin [at] mcgill.ca (Wayne Sossin)

Abstract: 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’s 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.