GABA, the primary inhibitory neurotransmitter, activates two distinct GABA(A) and GABA(B) receptors in the brain. Spontaneously firing dopamine neurons in the midbrain express both GABA(A) and GABA(B) receptors in the soma and dendrites. At least 70 % of the afferents to substantianigra dopamine neurons are GABAergic and many excitatory and inhibitory afferent inputs harmonically regulate firing activities. However, the distribution of these GABA receptors in the soma and dendrites and their roles in the regulation of spontaneous firing are still not clear in the dopamine neurons. Therefore, using a patch-clamp recording and GABA-uncaging techniques, we studied regional actions of GABA receptors on the spontaneous firing in acutely isolated dopamine neurons from the rat.
Application of either isoguvacine hydrochloride, a GABA(A) receptor agonist, or baclofen, a GABA(B) receptor agonist, completely suppressed spontaneous firing in the dopamine neurons. In addition, GABA was able to completely inhibit spontaneous firing under the presence of either GABA(A) receptor antagonist or GABA(B) receptor antagonist, suggesting that spontaneous firing can be inhibited by activation of only one type of GABA receptors. When we stimulated a various part of a dopamine neuron with caged GABA, activation of GABA receptors in any part of a neuron, such as the soma, proximal dendritic, and distal dendritic regions, inhibited spontaneous firing completely. However, in the soma, activation of GABA(A) or GABA(B) receptors equally suppressed spontaneous firing, but in the proximal and distal dendrites, GABA(B) receptors more strongly inhibited spontaneous firing than GABA(A) receptors. From these data, we conclude that the spontaneous firing of dopamine neurons could be arrested by the inhibitory action of both GABA(A) and GABA(B)receptors, equally, in the soma and in a GABA(B)-dominant way in the dendrites.