Most of the research that has been carried out in my laboratory in 1998 aimed at elucidating various aspects of the connectivity, synaptic chemistry and receptor localization in the monkey basal ganglia. We also wrote two extensive reviews that summarized our current view of the synaptic circuitry of the basal ganglia. We collaborated with colleagues in Canada in experiments relating to the synaptic connectivity of the amygdala in cats. In collaboration with Dr. Michael Kuhar, we looked at the subcellular localization and synaptic connectivity of CART peptides in the rodent and monkey brains. Finally, we also collaborated with the team of Dr. Jeffrey Conn to look at the functional interactions between group I metabotropic glutamate receptors and NMDA receptors. The main findings of these studies are summarized as follows (1) We showed that the inputs from the intralaminar thalamic nuclei are differentially distributed among subpopulations of striatal interneuro ns, whic h suggests a high degree of specificity in the processing of thalamic information by striatal neurons. (2) In collaboration with Dr. Denis Par? in Laval University, Qu?bec, Canada, we pursued our analysis of the synaptic organization of intrinsic and extrinsic connections of amygdaloid nuclei in cats. Our most recent findings indicate that parvalbumin-immunoreactive GABAergic interneurons are a major target of excitatory afferents in the basolateral amygdaloid nuclei. This provides essential anatomical data to elucidate the neuronal mechanisms that underlie the inhibitory network of the amygdala. (3) In collaboration with Dr. Michael Kuhar at the Yerkes Center, we analyzed the distribution of a novel family of peptides, Cocaine- and Amphetamine-Regulated Transcript (CART) peptides, in the nucleus accumbens, the gut and the hypothalamus, and found that CART is expressed in specific populations of chemically characterized neurons in both the central and peripheral nervous system. We also showed that CART peptides interact with neuropeptide Y in the paraventricular hypothalamic nucleus, which probably plays a major role in controlling feeding behavior. The results of these studies will help to understand better the role of CART peptides in the periphery, but also in the centrally mediated phenomenon of addiction to drugs of abuse and food ingestion. (4) We provided the first evidence that kainate receptors are expressed in glutamatergic terminals from the cerebral cortex in the monkey striatum. These findings support the hypothesis that an abnormal regulation of kainate receptor expression may be involved in mediating cell death in Huntington's disease. (5) In collaboration with Dr Jeffrey Conn, we showed that NMDA and the group I metabotropic glutamate receptor subtype, mGluR5, are co-expressed in individual spines and dendrites of pyramidal neurons in the rat neocortex and hippocampus. These anatomical data are supported by functional in vitro studies showi ng that NMDA receptor activation modulates mGluR5 function by reversing desensitization. FUNDING NINDS 1 R01 NS37948-01 $ 99,774 7/01/97 -- 6/30/02 NINDS 1 R01 NS37423-01 $134,215 5/01/98 -- 4/30/03 AM Parkinson Disease Association $ 25,000 9/01/97 -- 8/31/98 Internal Funds / Dept. Neurology, Emory University PUBLICATIONS Alagarsamy, S., Rouse, S.T., Gereau IV, R.W., Heinemann, S.F., Smith, Y. and Conn, P.J. Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Ann. N.Y. Acad. Sci. USA (In press). Charara, A., Blankstein, E. and Smith, Y. Pre-synaptic kainate receptors in the monkey striatum. Neuroscience (In press). Par?, D. and Smith, Y. Intra-amygdaloid connections Similarities between rats and cats. Trends Neurosci. 21:240-241, 1998. Sidib?, M. and Smith, Y. Thalamic inputs to striatal interneurones in monkeys Synaptic organization and co-localization of calcium binding proteins. Neuroscience (In press). Smith, Y., Par?, J.-F. and Par?, D. The intra-amygdaloid inhibitory network Ultrastructural organization of parvalbumin-immunopositive elements. J. Comp. Neurol. 391:164-179, 1998. Smith, Y., Shink, E., Bevan, M.D. and Bolam, J.P. Synaptology of the direct and indirect striatofugal pathways. Neuroscience 86:353-387, 1998. Smith, Y., Shink, E. and Sidib?, M. Neuronal circuitry and synaptic connectivity of the basal ganglia. In Neurosurgery Clinics of North America Surgical Treatment of Movement Disorders, Vol. 9, R.A.E. Bakay (Ed.). W.B. Saunders Co., Philadelphia, pp. 203-222, 1998.
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