Regional difference in spontaneous firing inhibition by GABAA and GABAB receptors in nigral dopamine neurons

Abstract

GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both GABA_A and GABA_B receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either GABA_A receptors or GABA_B receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either GABA_A or GABA_B receptor equally suppressed spontaneous firing in the soma, whereas GABA_B receptor inhibited spontaneous firing more strongly than GABA_A receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.

Keywords: Dopamine neuron; GABA; GABA receptor distribution; Somatodendritic balance; Spontaneous firing inhibition.