Electrophysiological studies of rat substantia nigra neurons in an in vitro slice preparation after middle cerebral artery occlusion

We studied sequential changes in electrophysiological profiles of the ipsilateral substantia nigra neurons in an in vitro slice preparation obtained from the middle cerebral artery-occluded rats. Histological examination revealed marked atrophy and neurodegeneration in the ipsilateral substantia nigra pars reticulata at 14 days after middle cerebral artery occlusion. Compared with the control group, there was no significant change in electrical membrane properties and synaptic responses of substantia nigra pars reticulata neurons examined at one to two weeks after middle cerebral artery occlusion. On the other hand, there was a significant increase in the input resistance and spontaneous firing rate of substantia nigra pars compacta neurons at 13-16 days after middle cerebral artery occlusion. Furthermore, inhibitory postsynaptic potentials evoked by stimulation of the subthalamus in substantia nigra pars compacta neurons was suppressed at five to eight days after middle cerebral artery occlusion. At the same time excitatory postsynaptic potentials evoked by the subthalamic stimulation was increased. Bath application of bicuculline methiodide (50 microM), a GABA(A) receptor antagonist, significantly increased the firing rate of substantia nigra pars compacta neurons from intact rats. These results strongly suggest that changes in electrophysiological responses observed in substantia nigra pars compacta neurons is caused by degeneration of GABAergic afferents from the substantia nigra pars reticulata following middle cerebral artery occlusion. While previous studies indirectly suggested that hyperexcitation due to deafferentation from the neostriatum may be a major underlying mechanism in delayed degeneration of substantia nigra pars reticulata neurons after middle cerebral artery occlusion, the present electrophysiological experiments provide evidence of hyperexcitation in substantia nigra pars compacta neurons but not in pars reticulata neurons at the chronic phase of striatal infarction.