Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening.

Abstract:

:Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glutamatergic activity at individual dendritic spines leads to synapse-specific synaptic weakening and spine shrinkage on CA1 neurons in the hippocampus. We found that shrinkage of individual spines in response to low-frequency glutamate uncaging is saturable, reversible, and requires NMDA receptor activation. Notably, shrinkage of large spines additionally requires signaling through metabotropic glutamate receptors (mGluRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs), supported by higher levels of mGluR signaling activity in large spines. Our results support a model in which signaling through both NMDA receptors and mGluRs is required to drive activity-dependent synaptic weakening and spine shrinkage at large, mature dendritic spines when neural circuits undergo experience-dependent modification.

authors

Oh WC,Hill TC,Zito K

doi

10.1073/pnas.1214705110

subject

Has Abstract

pub_date

2013-01-22 00:00:00

pages

E305-12

issue

4

eissn

0027-8424

issn

1091-6490

pii

1214705110

journal_volume

110

pub_type

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