Genetic inhibition of glutamate allosteric potentiation of GABA_ARs in mice results in hyperexcitability, leading to neurobehavioral abnormalities.

ABSTRACT: The imbalance between neuronal excitation and inhibition (E/I) in neural circuit has been considered to be at the root of numerous brain disorders. We recently reported a novel feedback crosstalk between the excitatory neurotransmitter glutamate and inhibitory γ-aminobutyric acid type A receptor (GABA_AR)-glutamate allosteric potentiation of GABA_AR functions through a direct binding of glutamate to the GABA_AR itself. Here, we investigated the physiological significance and pathological implications of this cross-talk by generating the β3_E182G knock-in (KI) mice. We found that β3_E182G KI, while had little effect on basal GABA_AR-mediated synaptic transmission, significantly reduced glutamate potentiation of GABA_AR-me

SUBMITTER: Du Y 

PROVIDER: S-EPMC10123808 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature