Stimulation of substantia nigra pars reticulata enhances dentate granule cell excitability

We studied the effects of electrical and chemical stimulation of the substantia nigra (SN) on the dentate granule cell (DGC) response to perforant path stimulation. Studies were carried out in both pentobarbital anesthetized and awake freely moving rats. Chemical stimulation was achieved by microinjection of N-methyl-D,L-aspartate (NMDA), an excitatory amino acid. Electrical preconditioning stimulation applied to the area of the SN, but not dorsal to SN, increased the excitability of DGCs. Intracerebral microinjection of NMDA into the contralateral SN pars reticulata (SNR), but not into SN pars compacta or cerebral peduncle, also produced a marked and reversible enhancement of DGC excitability. In both instances, the increased DGC excitability consisted of increased amplitude of the perforant path evoked population spike without change in the slope of the population excitatory postsynaptic potential (pEPSP). We interpret the data to indicate that increasing the output of the SNR increases the excitability of the DGCs, a limbic neuronal population regulating information transfer through hippocampal pathways. Together with our previous finding that decreasing the output of SNR suppressed limbic seizures, these data demonstrate that the SNR exerts a powerful influence on limbic system excitability. Delineating the anatomic pathway mediating this influence could provide valuable insight into the mechanisms underlying basal ganglia-limbic interactions in both physiologic and pathologic conditions.