Abstracts

Rationale: The substantia nigra pars reticulata (SNR) is a major output structure of the basal ganglia and plays an important role in the control of epileptic seizures especially via GABAA receptors. It has been divided into two topographically distinct GABAA-sensitive regions. In adult male rats, activation of GABAA receptors in the anterior SNR region is associated with anticonvulsant effects, whereas in the posterior SNR region, it is associated with proconvulsant effects. The region specific GABAA mediated effects may utilize distinct projections. In this study, we determined the afferent and the efferent projections of the anterior and posterior SNR. Methods: The retrograde tracer ‘fluorogold (FG)’ and the mixed anterograde and retrograde tracer ‘biotinylated dextran amine (BDA)’ were stereotactically injected into the anterior or posterior SNR by iontophoresis through a glass micropipette (tip diameter 25-50 µm). Following a survival period of 7-10 days, serial 40 µm coronal brain sections were obtained. The FG labeled neurons were evaluated under a fluorescence equipped microscope whereas the BDA labeled axon terminals were examined under a light microscope. Results: The afferent inputs into the SNR did not show any differences between the anterior and posterior regions. FG injections into the anterior or posterior SNR showed labelled neurons in the incular, cingulate, perirhinal and somatosensory cortices, striatum, lateral globus pallidus, subthalamic nucleus, zona inserta, dorsal raphe nucleus and pontine reticular formation. The efferent projections from the SNR were also similar from anterior and posterior SNR regions. BDA injections into either of SNR region showed labelled axon terminals in the ventromedial, centromedial and parafascicular thalamic nuclei, intermediate layer of the superior colliculus and pedunculopontine tegmental nucleus. However, labelled axon terminals were detected in the mediodorsal thalamic nucleus following BDA injection into the anterior but not the posterior SNR region. Conclusions: The results suggest that the efferent projections to the mediodorsal thalamic nucleus may play an important role in the SNR-mediated anticonvulsant effects following GABAA receptor activation in the anterior SNR region.