| First Author | Sanderson JL | Year | 2016 |
| Journal | Neuron | Volume | 89 |
| Issue | 5 | Pages | 1000-15 |
| PubMed ID | 26938443 | Mgi Jnum | J:230855 |
| Mgi Id | MGI:5766386 | Doi | 10.1016/j.neuron.2016.01.043 |
| Citation | Sanderson JL, et al. (2016) NMDA Receptor-Dependent LTD Requires Transient Synaptic Incorporation of Ca(2+)-Permeable AMPARs Mediated by AKAP150-Anchored PKA and Calcineurin. Neuron 89(5):1000-15 |
| abstractText | 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. |
