GABAmediated

GABAmediated describes cellular, synaptic, and network processes governed by gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter of the mammalian central nervous system. Through its action, GABA reduces neuronal excitability and helps shape tone, rhythm, and synchronization across brain circuits.

GABA acts on two major receptor families: GABA-A, which is ionotropic and mediates fast inhibitory synaptic transmission by opening chloride channels, and GABA-B, which is metabotropic and produces slower, longer-lasting inhibition via G-protein coupled mechanisms affecting potassium and calcium conductances. A third receptor, GABA-C (GABA_A-ρ), is also present in some regions and contributes to inhibition.

GABA is synthesized from glutamate by glutamic acid decarboxylase (GAD65/67) and released from presynaptic terminals. Termination of GABA signaling occurs mainly through reuptake by GABA transporters (GAT-1, GAT-3) and subsequent metabolism by GABA transaminase (GABA-T). Extrasynaptic and tonic inhibition can arise from ambient GABA acting on high-affinity receptors.

In development, GABA can be excitatory due to immature chloride buffering, but typically becomes inhibitory as chloride transporter expression changes. In adults, GABA-mediated inhibition balances excitatory activity and is crucial for sleep regulation, motor control, anxiety modulation, and seizure suppression.

Pharmacologically, agents that enhance GABAergic transmission include benzodiazepines and barbiturates (GABA-A modulators), baclofen (GABA-B agonist), and certain anticonvulsants and anesthetics. Dysfunctions in GABAergic signaling are implicated in epilepsy, anxiety disorders, insomnia, and several movement disorders.