| First Author | Davenport CM | Year | 2021 |
| Journal | Neuron | Volume | 109 |
| Issue | 1 | Pages | 123-134.e4 |
| PubMed ID | 33096025 | Mgi Jnum | J:300549 |
| Mgi Id | MGI:6503524 | Doi | 10.1016/j.neuron.2020.09.037 |
| Citation | Davenport CM, et al. (2021) Relocation of an Extrasynaptic GABAA Receptor to Inhibitory Synapses Freezes Excitatory Synaptic Strength and Preserves Memory. Neuron 109(1):123-134.e4 |
| abstractText | The excitatory synapse between hippocampal CA3 and CA1 pyramidal neurons exhibits long-term potentiation (LTP), a positive feedback process implicated in learning and memory in which postsynaptic depolarization strengthens synapses, promoting further depolarization. Without mechanisms for interrupting positive feedback, excitatory synapses could strengthen inexorably, corrupting memory storage. Here, we reveal a hidden form of inhibitory synaptic plasticity that prevents accumulation of excitatory LTP. We developed a knockin mouse that allows optical control of endogenous alpha5-subunit-containing gamma-aminobutyric acid (GABA)A receptors (alpha5-GABARs). Induction of excitatory LTP relocates alpha5-GABARs, which are ordinarily extrasynaptic, to inhibitory synapses, quashing further NMDA receptor activation necessary for inducing more excitatory LTP. Blockade of alpha5-GABARs accelerates reversal learning, a behavioral test for cognitive flexibility dependent on repeated LTP. Hence, inhibitory synaptic plasticity occurs in parallel with excitatory synaptic plasticity, with the ensuing interruption of the positive feedback cycle of LTP serving as a possible critical early step in preserving memory. |
