Abstracts

The substantia nigra pars reticulata (SNR) is important for seizure control. Infusions of GABA(A) receptor modulators, like muscimol, in rat SNR have age, sex and region specific effects on the threshold to flurothyl-induced seizures (Veliskova [amp] Moshé, 2001). At postnatal day 15 (PN15), muscimol infusions in the SNR are proconvulsant in males but have no effect in females. Muscimol infusions in PN30 male and female anterior SNR are anticonvulsant. In contrast, when infused in the posterior SNR of PN30 rats, muscimol has proconvulsant effects in males but no effect in females. The development of the muscimol-sensitive proconvulsant properties of the PN15 male SNR requires the testosterone surge, which occurs in newborn males. To test whether the divergent effects of muscimol in SNR mediated seizure control could be related to different GABA(A) receptor subunit composition, we studied the expression of the delta subunit in the SNR of PN15 and PN30 male and female rats. The delta subunit is contained in extrasynaptic GABA(A) receptors that mediate tonic inhibition and confers responsiveness to neurosteroid modulation. Adjacent sagittal SNR sections from PN15 and PN30 male and female rats were stained either with immunochemistry for the delta subunit of GABA(A) receptors (antibody was a gift by Dr G. Sperk, Germany) or with Nissl method. Cellular expression of delta-immunoreactivity (delta-ir) in anterior and posterior SNR neurons was compared using signal densitometry. Cell counting of delta-ir or Nissl-stained anterior or posterior SNR neurons was done on comparable sections from each brain. 1) PN15 rat SNR neurons had more somatic delta-ir than PN30 rats in both sexes and regions. 2) PN15 rats had more delta-ir SNR neurons than PN30 same-sex rats. 3) In the anterior SNR, a greater percentage of PN15 SNR neurons expressed delta-ir than the PN30 SNR, in both sexes. 4) In the posterior SNR, the percent of SNR neurons that were delta-ir was similar in all groups. 5) There were no sex differences in the numbers of delta-ir SNR neurons between groups. Delta-ir expression decreases with age in rat SNR. In the anterior SNR, an age-related decrease in both cellular expression and number of delta-ir SNR neurons occurs. In the posterior SNR, there is a decrease in cellular expression of delta-ir, but no change in delta-ir neuronal counts. The age-related reduction in delta-ir may contribute to the disappearance of the proconvulsant properties of the muscimol-sensitive male PN15 SNR neurons and the development of the anticonvulsant properties of the PN30 anterior SNR, in both sexes. (Supported by NIH NINDS grants NS048856 (NSADA) (HH), NS20253 (SLM), NS045243 (ASG).)