Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.

ABSTRACT: α5 subunit-containing GABA type-A receptors (α5 GABA_ARs) are enriched in the hippocampus and play critical roles in neurodevelopment, synaptic plasticity, and cognition. α5 GABA_AR preferring negative allosteric modulators (α5 NAMs) show promise mitigating cognitive impairment in preclinical studies of conditions characterized by excess GABAergic inhibition, including Down syndrome and memory deficits post-anesthesia. However, previous studies have primarily focused on acute application or single-dose α5 NAM treatment. Here, we measured the effects of chronic (7-day) in vitro treatment with L-655,708 (L6), a highly selective α5 NAM, on glutamatergic and GABAergic synapses in rat hippocampal neurons. We previously showed that 2-day in vitro treatment with L6 enhanced sy

SUBMITTER: Nuwer JL 

PROVIDER: S-EPMC10527172 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature