Long-range effects of GABAergic inhibition in gerbil primary auditory cortex

Throughout the literature, the effects of iontophoretically applied neurotransmitter agonists or antagonists on the local activity of neurons are typically studied at the site of drug application. Recently, we have demonstrated long-range inhibitory interactions within the primary auditory cortex (AI) that are effective in complex acoustic situations. To further characterize this long-range functional connectivity, we here report the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and the GABA(A) antagonist gabazine (SR 95531) on neuronal activity as a function of distance from the application site reaching beyond the diffusion radius of the applied drug. Neuronal responses to pure tone stimulation were simultaneously recorded at the application site and four additional sites, at distances between 300 and 1350 microm from the application site. We found that whereas application of GABA during best frequency (BF) stimulation in general led to a decrease, and gabazine to an increase, in neuronal activity at the application site, a considerable number of units at remote recording sites showed effects opposite to these local, drug-induced effects. These effects were seen both in spiking activity and in amplitudes of local field potentials. At all locations, the effects varied as a function of pure tone stimulation frequency, pointing to a Mexican-hat-like input function resulting from thalamic inputs to the BF region of the cortical neurons and intracortical interconnections projecting to off-BF regions of the neurons. These data demonstrate the existence of long-range, inhibitory interactions within the gerbil AI, realized either by long-range inhibitory projections or by long-range excitatory projections to local inhibitory interneurons.