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Neuron. 2016 Mar 2;89(5):1000-15. doi: 10.1016/j.neuron.2016.01.043.

NMDA Receptor-Dependent LTD Requires Transient Synaptic Incorporation of Ca²⁺-Permeable AMPARs Mediated by AKAP150-Anchored PKA and Calcineurin.

Author information

1
Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19th Avenue, Aurora, CO 80045, USA.
2
Department of Pharmacology, University of Colorado School of Medicine, 12800 East 19th Avenue, Aurora, CO 80045, USA; Program in Neuroscience, University of Colorado School of Medicine, 12800 East 19th Avenue, Aurora, CO 80045, USA. Electronic address: mark.dellacqua@ucdenver.edu.

Abstract

Information processing in the brain requires multiple forms of synaptic plasticity that converge on regulation of NMDA and AMPA-type glutamate receptors (NMDAR, AMPAR), including long-term potentiation (LTP) and long-term depression (LTD) and homeostatic scaling. In some cases, LTP and homeostatic plasticity regulate synaptic AMPAR subunit composition to increase the contribution of Ca(2+)-permeable receptors (CP-AMPARs) containing GluA1 but lacking GluA2 subunits. Here, we show that PKA anchored to the scaffold protein AKAP150 regulates GluA1 phosphorylation and plays a novel role controlling CP-AMPAR synaptic incorporation during NMDAR-dependent LTD. Using knockin mice that are deficient in AKAP-anchoring of either PKA or the opposing phosphatase calcineurin, we found that CP-AMPARs are recruited to hippocampal synapses by anchored PKA during LTD induction but are then rapidly removed by anchored calcineurin. Importantly, blocking CP-AMPAR recruitment, removal, or activity interferes with LTD. Thus, CP-AMPAR synaptic recruitment is required to transiently augment NMDAR Ca(2+) signaling during LTD induction.

PMID:
26938443
PMCID:
PMC4914360
[Available on 2017-03-02]
DOI:
10.1016/j.neuron.2016.01.043
[Indexed for MEDLINE]
Free PMC Article

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