The effects of dopamine-depleting brain lesions on the electrophysiological activity of rat substantia nigra dopamine neurons

Abstract

Extensive damage to the nigrostriatal dopamine (DA) system initiates a number of compensatory changes that may be involvei in counterbalancing the effects of the lesion. In this study, we examined whether changes in the electrophysiological activity of the remaining DA cells play a role in compensating for 6-hydroxydopamine (6-OHDA)-induced depletions of striatal DA. DA cell activity in lesioned rats was assessed along three dimensions: (1) the relative proportion of the remaining DA neurons firing spontaneously, (2) their firing rate, and (3) their firing pattern. Histofluorescence studies revealed a sparing of DA neurons in the midbrain of 6-OHDA-lesioned rats relative to the levels of DA remaining in the striatu. With respect to DA cell activity, depletions of up to 96% of striatal DA did not result in substantial alterations in the proportion of DA neurons active, their mean firing rate, or their firing pattern. Increases in these parameters only occurred when striatal DA depletions exceeded 96%. These results suggest that the biochemical and receptor compensations produced in the DA system in response to injury are of sufficient magnitude to allow the DA cells to maintain baseline levels of activity. In this way, the remaining DA neurons would maintain the wide dynamic range of electrophysiological responsivity that may be necessary for the normal function of the extrapyramidal motor system.