Alteration of ambient GABA by phasic and tonic neuronal activation.

Neurons of primary auditory cortex (AI) emit spikes (action potentials) in two distinct manners, responding to sounds in an onset or a sustained manner. The former AI neurons are called phasic cells and the latter tonic cells. The phasic cells generate spikes for a brief time period (less than hundreds of milliseconds) at the onset of an auditory stimulus (e.g., a tone frequency sound), and the tonic cells continuously generate spikes throughout the stimulation period. Simulating a neural network model of AI, we investigated whether and how the onset discharges influence the sustained discharges that are believed to play a central role in encoding auditory information. Onset discharges, triggered by a phasic input, briefly excited GABAergic interneurons and transiently increased the level of ambient GABA, which was immediately recognized by extrasynaptic GABA(a) receptors and provided inhibitory currents into neurons. The transient alteration of ambient GABA allowed tonic cells to respond selectively to a tonic input. The timing of phasic input relative to a tonic one had a great impact on the responsiveness of tonic cells. We found optimal timing for the best selective responsiveness: phasic input preceding tonic input by several tens of milliseconds. Offset discharges induced by a secondary input to phasic cells, applied at the end of the tonic input period, suddenly terminated the sustained discharges and allowed the network to return rapidly to the ongoing-spontaneous neuronal state. We suggest that the transporter-mediated alteration of ambient GABA, triggered by onset discharges, may improve the response property of AI neurons. Offset discharges may have a role in resetting AI neurons so that they can prepare for the next auditory input.