Identification of a subpopulation of substantia nigra pars compacta gamma-aminobutyric acid neurons that is regulated by basal ganglia activity.

Abstract

In this report, the authors provide a novel description of a population of gamma-aminobutyric acid-containing neurons in the substantia nigra, pars compacta (SNC). By using metabolic mapping of the immediate-early gene, c-fos, the activation pattern of these cells was characterized with respect to basal ganglia stimulation. Dopaminergic stimulation with d-amphetamine or apomorphine induced Fos expression in the central region of the SNC. However, lesions of the nigrostriatal dopamine pathway significantly reduced d-amphetamine- and apomorphine-induced Fos expression in the ipsilateral and contralateral SNC, respectively. Suppression of stimulant-induced Fos expression in the striatum, using antisense oligodeoxynucleotides, also eliminated Fos expression in the ipsilateral SNC, indicating that striatal efferent projections are involved in the activation of these cells. Double-labeling immunohistochemistry revealed that the Fos-positive cells did not express tyrosine hydroxylase but were immunoreactive for glutamic acid decarboxylase. Retrograde labeling of nigrostriatal neurons, combined with Fos immunofluorescence, revealed that these Fos-positive cells did not project to the striatum. Thus, these neurons do not appear to comprise a nondopaminergic nigrostriatal circuit but likely represent locally-projecting interneurons of the substantia nigra.