GABA uptake via GABA transporter-1 modulates GABAergic transmission in the immature hippocampus

Abstract

GABA uptake limits GABA actions during synaptic responses when the density of active release sites is high or multiple axons are synchronously activated. GABA transporter-1 (GAT-1) is the main neuronal GABA transporter subtype and is already expressed in the early postnatal rat hippocampus. However, previous studies have demonstrated little functional role for the transporter during this developmental period. We used whole-cell voltage-clamp and field-potential recordings in hippocampal slices of neonatal rats (postnatal day 4-5) to study whether GAT-1 plays a role in GABAergic transmission during spontaneous population oscillations, which are seen as "giant depolarizing potentials" (GDPs) in intracellular recordings. We show that the GDP-associated GABAergic current observed in CA3 pyramidal neurons is strongly enhanced by the GAT-1-specific blocker NO-711 (1-[2-[[(diphenylmethylene)imino] oxy]ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride). Our results indicate a novel role for GAT-1 in the control of endogenous activity of the immature hippocampus.