2019
DOI: 10.1126/science.aav1483
|View full text |Cite
|
Sign up to set email alerts
|

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

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 i… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

3
81
0

Year Published

2019
2019
2023
2023

Publication Types

Select...
8
1

Relationship

0
9

Authors

Journals

citations
Cited by 118 publications
(84 citation statements)
references
References 50 publications
3
81
0
Order By: Relevance
“…Since learning and memory formation, as well as the expression of long-term potentiation (LTP), are associated with increased levels of GluA2/AMPARs at post-synaptic densities, this particular forgetting process thus resembles the reversal of enhanced connectivity Nadel and colleagues had envisioned in 1984. Our findings have recently been replicated and extended by others who identified the calcium sensor synaptotagmin-3 as a key element in reducing the expression of AMPARs during the active decay of long-term memories (Awasthi et al, 2019). Thus, the current evidence strongly suggests that long-term memories are lost by a constitutive process that progressively disassembles the morphological changes to synapses that emerged during learning and memory formation, and that this process involves calcium signaling.…”
Section: Introductionsupporting
confidence: 85%
“…Since learning and memory formation, as well as the expression of long-term potentiation (LTP), are associated with increased levels of GluA2/AMPARs at post-synaptic densities, this particular forgetting process thus resembles the reversal of enhanced connectivity Nadel and colleagues had envisioned in 1984. Our findings have recently been replicated and extended by others who identified the calcium sensor synaptotagmin-3 as a key element in reducing the expression of AMPARs during the active decay of long-term memories (Awasthi et al, 2019). Thus, the current evidence strongly suggests that long-term memories are lost by a constitutive process that progressively disassembles the morphological changes to synapses that emerged during learning and memory formation, and that this process involves calcium signaling.…”
Section: Introductionsupporting
confidence: 85%
“…Subunits of the AMPA receptors are subjected to tight regulation because of their pivotal roles in synaptic plasticity. Regulation includes phosphorylation and translocation to the membrane (Park et al, 2006;Shi et al, 1999), endocytosis (Awasthi et al, 2019), and local translation (Ju et al, 2004;Kacharmina, Job, Crino, & Eberwine, 2000). GluA2 is one of the main AMPA receptor subunits expressed in the hippocampus (Lu et al, 2009), and mRNAs of GluA1 and GluA2 are found in dendrites where they are synthesized locally and incorporated into the membrane at or near synapses (Ju et al, 2004).…”
Section: Ad Pathology Is Differentially Affected By Mir-181a Inhibimentioning
confidence: 99%
“…These findings indicated a role for synaptotagmin-11 in the inhibition of endocytosis and vesicle recycling in neurons. Another member of the synaptotagmin family, Syt3 was shown to interact with GluA2 receptors in postsynaptic membranes, where it enhanced the endocytosis of receptors in response to Ca 2+ , generating an activity-dependent decrease in synaptic strength (Awasthi et al, 2019). It would be interesting to test the idea that Syt11 in glioblastoma slows endocytosis of GluA2 receptors, promoting glutamate-driven signaling.…”
Section: Synaptic Proteins Enriched In Glioblastomamentioning
confidence: 99%