GABA Transporter Preserving Ongoing Spontaneous Neuronal Activity at Firing Subthreshold

Abstract

There has been compelling evidence that the GABA transporter is crucial not only for removing gamma-aminobutyric acid (GABA) from but also releasing it into extracellular space, thereby clamping ambient GABA (GABA in extracellular space) at a certain level. The ambient GABA is known to activate extrasynaptic GABA receptors and provide tonic inhibitory current into neurons. We investigated how the transporter regulates the level of ambient GABA, mediates tonic neuronal inhibition, and influences ongoing spontaneous neuronal activity. A cortical neural network model is proposed in which GABA transporters on lateral (L) and feedback (F) inhibitory (GABAergic) interneurons are functionally made. Principal (P) cell assemblies participate in expressing information about elemental sensory features. At membrane potentials below the reversal potential, there is net influx of GABA, whereas at membrane potentials above the reversal potential, there is net efflux of GABA. Through this transport mechanism, ambient GABA concentration is kept within a submicromolar range during an ongoing spontaneous neuronal activity time period. Here we show that the GABA transporter on L cells regulates the overall level of ambient GABA across cell assemblies, and that on F cells it does so within individual cell assemblies. This combinatorial regulation of ambient GABA allows P cells to oscillate near firing threshold during the ongoing time period, thereby reducing their reaction time to externally applied stimuli. We suggest that the GABA transporter, with its forward and reverse transport mechanism, could regulate the ambient GABA. This transporter-mediated ambient GABA regulation may contribute to establishing an ongoing subthreshold neuronal state by which the network can respond rapidly to subsequent sensory input.