NMDA Receptor-Dependent LTD Requires Transient Synaptic Incorporation of Ca²⁺-Permeable AMPARs Mediated by AKAP150-Anchored PKA and Calcineurin
| Autor: | Jennifer L, Sanderson, Jessica A, Gorski, Mark L, Dell'Acqua |
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| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Silver Staining musculoskeletal neural and ocular physiology Calcineurin Long-Term Synaptic Depression A Kinase Anchor Proteins Mice Transgenic Synaptic Potentials Cyclic AMP-Dependent Protein Kinases Hippocampus Receptors N-Methyl-D-Aspartate Electric Stimulation Article Mice Inbred C57BL Mice nervous system Mutation Synapses Animals Calcium Excitatory Amino Acid Agents Receptors AMPA Enzyme Inhibitors |
| Zdroj: | Neuron. 89(5) |
| ISSN: | 1097-4199 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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