Changes in firing rate and pattern of GABAergic neurons in subregions of the substantia nigra pars reticulata in rat models of Parkinson's disease

Abstract

The substantia nigra pars reticulata (SNr) plays a key role in the pathophysiology of Parkinson's disease (PD). It has been well documented that the SNr is not a homogeneous structure, and the lateral and medial subregions of the SNr receive different projections from the sensorimotor and limbic striatum, respectively. However, specific changes in firing activity of SNr subregions in PD remain unclear. In the present study, the spontaneous firing activity of GABAergic neurons in the lateral and medial SNr of rats with unilateral 6-hydroxydopamine lesions of the substantia nigra pars compacta (SNc) or medial forebrain bundle (MFB) has been examined. Extracellular recordings indicated that the firing rate of lateral SNr neurons increased significantly and firing pattern of these neurons changed towards more irregular and bursty after SNc or MFB lesions compared to normal rats. In contrast, the firing rate and pattern of medial SNr neurons in rats with SNc lesions were unaltered when compared with that of normal rats. However, MFB lesions in rats decreased the firing rate of medial SNr neurons and firing pattern of these neurons changed towards more bursty. In addition, SNc lesions in rats increased the firing rate of the neurons with regular and irregular firing patterns within lateral but not in medial SNr, while the firing rate of the neurons within lateral and medial SNr with each firing pattern was not altered after MFB lesions. These results suggest that GABAergic neurons of SNr subregions have differential change of firing activity in the pathophysiology of PD.