DIFFERENTIAL DISTRIBUTION OF GLUTAMIC-ACID DECARBOXYLASE-65 AND GLUTAMIC-ACID DECARBOXYLASE-67 MESSENGER-RNAS IN THE ENTOPEDUNCULAR NUCLEUSOF THE RAT

The entopeduncular nucleus is one of the major output nuclei of the ba sal ganglia, with topographically organized projections to both motor and limbic structures. Neurons of the entopeduncular nucleus use GABA as the principal transmitter, and glutamic acid decarboxylase (the GAB A synthetic enzyme) is widely distributed throughout the region. Previ ous studies have shown that glutamate decarboxylase exists in two form s (glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67), and that the messenger RNAs for these different enzymes are widely di stributed in rat brain. The purpose of the present experiment was to d escribe the distribution of glutamic acid decarboxylase-65 and glutami c decarboxylase-67 messenger RNAs throughout the entopeduncular nucleu s using recently developed oligodeoxynucleotide probes and in situ hyb ridization histochemical methods. In agreement with previous studies, northern analysis of rat brain poly(A)(+) messenger RNA preparations s howed that the glutamic acid decarboxylase-65 and glutamic acid decarb oxylase-67 probes used in the present study hybridized to messenger RN As of approximately 5.7 and 3.7 kb, respectively. Film autoradiographi c analysis revealed large region-dependent, isoform-specific differenc es in the levels of expression of the two messenger RNAs, with glutami c acid decarboxylase-65 messenger RNA predominating in rostral and med ial regions of the entopeduncular nucleus and glutamic acid decarboxyl ase-67 messenger RNA most abundant in the caudal region. Cellular anal ysis showed that these region-dependent differences in labelling were due to differences in the relative amounts of glutamic acid decarboxyl ase-65 and glutamic acid decarboxylase-67 messenger RNAs expressed per cell rather than the number of cells expressing each form of glutamic acid decarboxylase messenger RNA. The differences in the distribution of glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67 messenger RNAs are closely related to the organization of limbic and m otor circuits of the entopeduncular nucleus, suggesting that GABAergic transmission through the limbic pathway is regulated predominantly by glutamic acid decarboxylase-65, whereas glutamic acid decarboxylase-6 7 is of principal importance in the motor pathway. These data provide additional evidence that the neurons of the limbic and motor subregion s of the entopeduncular nucleus are neurochemically distinct. (C) 1997 IBRO.