Differential distribution of glutamate decarboxylase-65 and glutamate decarboxylase-67 messenger RNAs in the entopeduncular nucleus of the rat

• Published in: Neuroscience 1997-02, Vol.78 (1), p.87-97
• Main Authors: Yuan, P.-Q, Grånäs, C, Källström, L, Yu, J, Huhman, K, Larhammar, D, Albers, H.E, Johnson, A.E
• Format: Article
• Language: English
• Subjects: basal ganglia; entopeduncular nucleus; GABA; glutamate decarboxylase-65; glutamate decarboxylase-67; tardive dyskinesia
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(96)00593-3

The entopeduncular nucleus is one of the major output nuclei of the basal ganglia, with topographically organized projections to both motor and limbic structures. Neurons of the entopeduncular nucleus use GABA as the principal transmitter, and glutamate decarboxylase (the GABA synthetic enzyme) is widely distributed throughout the region. Previous studies have shown that glutamate decarboxylase exists in two forms (glutamate decarboxylase-65 and glutamate decarboxylase-67), and that the messenger RNAs for these different enzymes are widely distributed in rat brain. The purpose of the present experiment was to describe the distribution of glutamate decarboxylase-65 and glutamic decarboxylase-67 messenger RNAs throughout the entopeduncular nucleus using recently developed oligodeoxynucleotide probes and in situ hybridization histochemical methods. In agreement with previous studies, northern analysis of rat brain poly(A) + messenger RNA preparations showed that the glutamate decarboxylase-65 and glutamate decarboxylase-67 probes used in the present study hybridized to messenger RNAs of approximately 5.7 and 3.7 kb, respectively. Film autoradiographic analysis revealed large region-dependent, isoform-specific differences in the levels of expression of the two messenger RNAs, with glutamate decarboxylase-65 messenger RNA predominating in rostral and medial regions of the entopeduncular nucleus and glutamate decarboxylase-67 messenger RNA most abundant in the caudal region. Cellular analysis showed that these region-dependent differences in labelling were due to differences in the relative amounts of glutamate decarboxylase-65 and glutamate decarboxylase-67 messenger RNAs expressed per cell rather than the number of cells expressing each form of glutamate decarboxylase messenger RNA. The differences in the distribution of glutamate decarboxylase-65 and glutamate decarboxylase-67 messenger RNAs are closely related to the organization of limbic and motor circuits of the entopeduncular nucleus, suggesting that GABAergic transmission through the limbic pathway is regulated predominantly by glutamate decarboxylase-65, whereas glutamate decarboxylase-67 is of principal importance in the motor pathway. These data provide additional evidence that the neurons of the limbic and motor subregions of the entopeduncular nucleus are neurochemically distinct.