Sleep and wake cycles dynamically modulate hippocampal inhibitory synaptic plasticity

Sleep is an essential process that consolidates memories by modulating synapses through poorly understood mechanisms. Here, we report that GABAergic synapses in hippocampal CA1 pyramidal neurons undergo daily rhythmic alterations. Specifically, wake inhibits phasic inhibition, whereas it promotes tonic inhibition compared to sleep. We further utilize a model of chemically induced inhibitory long-term potentiation (iLTP) to examine inhibitory plasticity. Intriguingly, while CA1 pyramidal neurons in both wake and sleep mice undergo iLTP, wake mice have a much higher magnitude. We also employ optogenetics and observe that inhibitory inputs from parvalbumin-, but not somatostatin-, expressing interneurons contribute to dynamic iLTP during sleep and wake. Finally, we demonstrate that synaptic insertion of alpha 5-GABA(A) receptors underlies the wake-specific enhancement of iLTP at parvalbumin-synapses, which is independent of time of the day. These data reveal a previously unappreciated daily oscillation of inhibitory LTP in hippocampal neurons and uncover a dynamic contribution of inhibitory synapses in memory mechanisms across sleep and wake.

Automated summary

Sleep is an essential process for memory consolidation, and this study reveals the daily rhythmic alterations of GABAergic synapses in hippocampal CA1 pyramidal neurons. Wake promotes tonic inhibition and inhibits phasic inhibition compared to sleep. The study also demonstrates that inhibitory inputs from parvalbumin-expressing interneurons contribute to dynamic iLTP during sleep and wake. Additionally, synaptic insertion of alpha 5-GABA(A) receptors is found to underlie the wake-specific enhancement of iLTP at parvalbumin synapses, independent of the time of the day.