Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.
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.
Mesh Terms:
Animals, Calcium, Cells, Cultured, Endocytosis, Female, HEK293 Cells, Hippocampus, Humans, Immunohistochemistry, In Vitro Techniques, Long-Term Potentiation, Long-Term Synaptic Depression, Male, Maze Learning, Memory, Mice, Mice, Knockout, Neurons, Protein Transport, Rats, Wistar, Receptors, AMPA, Subcellular Fractions, Synapses, Synaptic Vesicles, Synaptosomes, Synaptotagmins, Transfection
Animals, Calcium, Cells, Cultured, Endocytosis, Female, HEK293 Cells, Hippocampus, Humans, Immunohistochemistry, In Vitro Techniques, Long-Term Potentiation, Long-Term Synaptic Depression, Male, Maze Learning, Memory, Mice, Mice, Knockout, Neurons, Protein Transport, Rats, Wistar, Receptors, AMPA, Subcellular Fractions, Synapses, Synaptic Vesicles, Synaptosomes, Synaptotagmins, Transfection
Science
Date: Jan. 04, 2019
PubMed ID: 30545844
View in: Pubmed Google Scholar
Download Curated Data For This Publication
254489
Switch View:
- Interactions 3