Peer-Reviewed Journal Details
Mandatory Fields
Awasthi A;Ramachandran B;Ahmed S;Benito E;Shinoda Y;Nitzan N;Heukamp A;Rannio S;Martens H;Barth J;Burk K;Wang YT;Fischer A;Dean C;
Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.
Optional Fields
Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.
Grant Details