Excitatory responses in the 'direct' striatonigral pathway: effect of nigrostriatal lesion

The existence of a striatonigral GABAergic projection that inhibits substantia nigra reticulata (SNr) cells has been well established. We report on electrophysiological evidence in the rat for a striatonigral excitatory pathway that affects 15% of all SNr cells. Using the antidromic response test to classify SNr cells in relation to their projecting nucleus, an excitatory striatonigral response was found in 57% of cells projecting to the pedunculopontine tegmental nucleus (PPTg) and 11% of cells projecting to the thalamus. SNr cells innervated by inhibitory or excitatory striatonigral inputs had a similar firing rate but a lower variation coefficient (VC) than SNr cells that did not respond to striatonigral inputs. The 6-hydroxydopamine (6-OHDA) degeneration of nigrostriatal dopaminergic cells (A9) induced an increase in the percentage of SNr cells excited from the striatum (52%) and in the VC, but no modification of the firing rate or of the number of spikes induced by each striatal stimulus. This increase in VC was found for the striatonigral inhibitory, but not for the striatonigral excitatory pathway. These data indicate that in addition to its inhibitory action, the direct striatonigral pathway has an excitatory activity that is particularly prominent for SNr cells projecting to the pedunculopontine nucleus. Because the percentage of SNr cells excited by this pathway was markedly increased by DA cell degeneration, our findings suggest that the excitatory striatonigral system could be involved in the pathophysiology of Parkinson's disease.