{"doi":"10.4103/1673-5374.373665","title":"GABAergic synaptic transmission and plasticity oscillate across sleep and wake","abstract":"Sleep is a widely expressed behavior across the animal kingdom. In addition to the numerous health benefits that are associated with sleep, it is believed that sleep plays a pivotal role in mental processes such as learning and memory. Indeed, it has been demonstrated that learning and memory benefit from sleep, whereas sleep loss causes cognitive impairment (Rasch and Born, 2013). Changing the strength of synapses, the connections between neurons, has been proposed to be the basic memory mechanism. Therefore, it is not surprising that many studies about the memory functions of sleep have focused on its effects on synapses. An influential hypothesis regarding the function of sleep in learning and memory is the synaptic homeostasis hypothesis, which proposes that wake increases overall excitatory synaptic strength due to ongoing learning and sleep renormalizes them to facilitate memory consolidation and integration (Tononi and Cirelli, 2014). This view has received support by findings in a number of studies showing molecular, morphological and electrophysiological changes indicative of excitatory synaptic weakening during sleep and strengthening during wake (Tononi and Cirelli, 2014). However, several recent studies have shown that sleep can potentiate excitatory synaptic transmission (Chauvette et al., 2012), or have no impact on excitatory synaptic strength (Cary and Turrigiano, 2021). These studies indicate complex mechanisms underlying the possible roles of sleep in regulating excitatory synapses. Of note, given a neuron typically receives thousands of synaptic inputs and the interactions between excitatory and inhibitory synaptic inputs determine the level of activity in it, neuronal communication across sleep and wake is probably regulated as a balance between excitatory and inhibitory influences. However, compared to extensive studies on excitatory synapses, much less is known about the regulation of inhibitory synapses by sleep. At inhibitory synapses, gamma-aminobutyric acid (GABA) released by presynaptic neurons diffuses across the synaptic cleft, the gap between the pre and post-synaptic neurons and binds to GABA type A (GABAA) receptor sitting at post-synaptic membranes, allows anions to enter the cell, and drives the membrane potential away from the threshold, making post-synaptic neurons less likely to generate action potentials. GABAARs can be classified as mediating either phasic or tonic inhibition. Specifically, in the hippocampus, phasic inhibition is primarily mediated by α1/α2-GABAARs, and tonic inhibition is mediated by extrasynaptic α4/α5-GABAARs. Recently we have employed a non-invasive sleep tracking system in real time to monitor the accumulation of sleep and wake and recorded GABAergic transmission in the mouse hippocampus, a brain area known to be required for memory consolidation and integration. We show 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. Consistent with the electrophysiological data, wake decreased synaptic expression of α1/α2-GABAARs but the increased surface expression of α4/α5-GABAARs in the hippocampus (Wu et al., 2022a). This distinction in the regulation of phasic and tonic forms of inhibition presumably implies a profound difference in the control of neuronal network function across sleep and wake. We speculate that the sleep-associated increase of phasic inhibition contributes to the generation of coherent rhythms of network activity, which may facilitate memory consolidation during sleep. The reduced tonic inhibition in sleep may compensate for the changes of phasic inhibition to maintain overall inhibitory tone to preserve the network stability. Synaptic plasticity has been proposed to be the cellular basis of learning and memory that involves diverse signaling pathways that lead to either strengthening or weakening of synapses","journal":"Neural Regeneration Research","year":2023,"id":383279,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.956,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247148,"name":"Wei Lü","orcid":"0000-0001-6668-8432","position":1,"is_corresponding":false},{"id":291743,"name":"Kunwei Wu","orcid":"0000-0003-4074-0567","position":0,"is_corresponding":true}],"reference_count":14,"raw_metadata":null,"created_at":"2026-07-19T01:17:25.158896Z","pmid":"37449604","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}