Format

Send to

Choose Destination
Science. 2019 Jan 4;363(6422). pii: eaav1483. doi: 10.1126/science.aav1483. Epub 2018 Dec 13.

Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.

Author information

1
Trans-synaptic Signaling Group, European Neuroscience Institute, 37077 Goettingen, Germany.
2
German Center for Neurodegenerative Disease, 37075 Goettingen, Germany.
3
Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, 37075 Goettingen, Germany.
4
Synaptic Systems GmbH, 37079 Goettingen, Germany.
5
Brain Research Center and Department of Medicine, University of British Columbia, Vancouver, BC V6T2B5, Canada.
6
Trans-synaptic Signaling Group, European Neuroscience Institute, 37077 Goettingen, Germany. c.dean@eni-g.de.
#
Contributed equally

Abstract

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.

Comment in

PMID:
30545844
DOI:
10.1126/science.aav1483
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center