Synaptic Calcineurin Affects LTP and LTD
نویسندگان
چکیده
Homomeric AMPA receptors (AMPARs) composed solely of GluA1 subunits are permeable to Ca , whereas heteromeric receptors containing GluR2 are not. PhosphorylationofGluA1bycAMP-dependentprotein kinase (PKA) in hippocampal neurons stabilizes Ca -permeable AMPARs in extrasynaptic membranes, where they can move into synapses during long-term potentiation (LTP). Dephosphorylation of GluA1 by calcineurin and other phosphatases causes endocytic removal of homomeric AMPARs, and this contributes to long-term depression (LTD). Calcineurin is ubiquitously expressed and must interact with A-kinase anchoring protein 150 (AKAP150) to remain near synapses. To selectively examine the synaptic role of calcineurin, therefore, Sanderson et al. generated knock-in mice in which normal AKAP150 was replaced by a form lacking the calcineurin-binding domain. Hippocampal LTD was disrupted in these mice, but LTP induced by strong stimulation was enhanced. Although LTD caused dephosphorylation of GluA1 in knock-in mice, phosphorylation recoveredmorequicklythannormal,suggesting synaptic calcineurin is required for persistent dephosphorylation of GluA1, which in turn is required for LTD. ΠDevelopment/Plasticity/Repair
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