CELLULAR-LOCALIZATION OF SYNAPTOTAGMIN-I, SYNAPTOTAGMIN-II, AND SYNAPTOTAGMIN-III MESSENGER-RNAS IN THE CENTRAL-NERVOUS-SYSTEM AND PITUITARY AND ADRENAL-GLANDS OF THE RAT

Three isoforms of synaptotagmin, a synaptic vesicle protein involved i n neurotransmitter release, have been characterized in the rat, althou gh functional differences between these isoforms have not been reporte d, In situ hybridization was used to define the localization of synapt otagmin I, II, and III transcripts in the rat CNS and pituitary and ad renal glands. Each of the three synaptotagmin genes has a unique expre ssion pattern. The synaptotagmin III gene is expressed in most neurons , but transcripts are much less abundant than the products of the syna ptotagmin I and II genes, A majority of neurons in the forebrain expre ssed both synaptotagmin I and III mRNAs while synaptotagmin II gene ex pression was confined to subsets of neurons in layers IV-VI of the cer ebral cortex, in the dentate granule cell region, the hilus, and the C A1-CA3 areas of the hippocampus. In the cerebellum, all three transcri pts were visualized in the granule cell layer. Furthermore, synaptotag min I probes revealed striking differences between distinct population s of neurons, as in addition to moderate labeling of granule cells, mu ch more prominent hybridization signals were detected on scattered cel l bodies likely to be Golgi interneurons. In the most caudal part of t he brain, synaptotagmin II transcripts were abundant and were coexpres sed with synaptotagmin III mRNAs. This pattern was found in putative m otoneurons of the spinal cord, suggesting that the two isoforms might be involved in exocytosis at the neuromuscular junction, Only synaptot agmin I mRNAs were detected in the anterior and intermediate pituitary and in adrenal medullary cells. These data reveal an unexpectedly sub tle segregation of the expression of synaptotagmin genes and the exist ence of multiple combinations of synaptotagmin isoforms which may prov ide diversity in the regulation of neurosecretion.