It is well established that gamma-aminoburyric acid (GABA) is an important inhibitory neurotransmitter in virtually every region of the CNS, including the rostral nucleus of the solitary tract (rNST). Interestingly, it appears that the effects of GABA are not limited to the modulation of the activity of mature neurons. Recent data indicate that GABA is also important in the regulation of neural development, first exerting a number of trophic influences on developing brain cells, then serving as an excitatory neurotransmitter and finally an inhibitory neurotransmitter. Unfortunately, we know very little about the factors that stimulate and regulate the developmental changes in GABAergic neurons. There is, however, limited but intriguing evidence that one important factor is the arrival of APPROPRIATE EXCITATORY INPUT. We propose that the protracted postnatal development of the gustatory system offers an excellent opportunity to study this phenomenon. Our studies are based on two hypotheses: 1) GABA functions as an excitatory as well as an inhibitory neurotransmitter during the early postnatal maturation of gustatory neurons in the rNST, with the development of GABA's predominantly inhibitory effect on taste-sensitive rNST neurons coinciding with an increase in the number of type A GABA receptors and a redistribution of type B GABA receptors; 2) The initial disposition and subsequent rearrangement of GABAergic synapses on gustatory neurons is dependent on appropriate primary afferent inputs. We will test these hypotheses with the following experiments: 1)Use light- and electron-microscopic immunohistochemistry to characterize the expression and disposition of type A and type B GABA receptors during postnatal development of the rNST; 2)Determine the effect of GABA and GABA receptor antagonists on the response properties of rNST neurons from early postnatal rats (using in vitro and in vivo recording techniques); 3)Determine the disposition of GABAergic synapses onto identified gustatory neurons during normal development of the rNST; 4)Examine the distribution of GABAergic synapses onto gustatory neurons following transection of the chorda tympani and/or glossopharyngeal nerves. We believe that the studies proposed in this application will yield significant and novel data regarding the development of inhibitory circuits in the central nervous system.
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