Significance The sensory areas of primate cerebral cortex are the major areas receiving impulses generated by innocuous and noxious stimuli applied to cutaneous and other tissues. The representations of the external world in these areas can be modified by sensory perturbations that modify cortical structure and function. The experiments seek to study the underlying molecular mechanisms that make this plasticity possible and the accompany synaptic changes that permit the cortex to adapt to changing inputs and to learn throughout the life of the individual. Objectives This study was designed to determine the effects of reduction in sensory input on expression of genes for the major neurotransmitter receptors in the cerebral cortex. Results Complementary RNA probes derived from complementary DNA specifically subcloned from monkey tissue were used to localize, by in situ hybridization histochemistry, the relatively rare (3, (3 and (1 subunit transcripts of the GABAA receptor in visual cortex and lateral geniculate nucleus of normal monkeys and in monkeys that had been deprived of vision in one eye. Overall, levels of (3, (3 and (1 subunit transcripts were very low. In the primary visual cortex (area 17) they were concentrated in layers II and VI and in a stratum of white matter subjacent to layer VI. The localization and density of the three messenger RNAs closely resembled those of other rare ((2, (5 and (1) transcripts but their distribution also overlapped that of the predominant (1, (2 and (2 subunit transcripts. In area 18, (3 and (3 transcript distribution resembled that in area 17, with the addition of a third band of hybridization in layer IV for (3, (1 subunit transcript localization in area 18 diffe red significantly from that in area 17, with increased expression restricted layer IV. In the dorsal lateral geniculate nucleus, (3, and (1 transcripts were expressed at low levels across all layers while (3 transcripts were restricted to the magnocellular layers. Following 15 and 18 day periods of monocular deprivation, induced by intravitreal injections of tetrodotoxin, levels of (3 receptor subunit transcripts showed modest reductions in layer VI of area 17 and in deprived geniculate laminae of adult animals. Reductions in (3 transcript levels were much more pronounced in layer IVCB of a five-month-old monkey deprived for the same time. Levels of (3 and (1 transcripts were unaffected by monocular deprivation in cortex and geniculate at any age. Taken together with studies of other GABAA receptor transcripts, these results demonstrate the heterogeneity of GABAA receptor messenger RNA expression in the monkey geniculo-striate pathway and the varied response to reduced neuronal ac tivity. Future Directions We will continue to use the monkey visual deprivation model to study activity-dependent expression of further neuroactive genes. KEY WORDS cerebral cortex, GABA, glutamate receptors, gene expression FUNDING NIH Grant NS21377 PUBLICATIONS Huntsman, M.M. and Jones, E.G. Expression of (3, (3 and (1 GABAA receptor subunit mRNAs in visual cortex and lateral geniculate nucleus of normal and monocularly deprived monkeys. Neuroscience 87:385-400, 1998. Jones, E.G., Tighilet, B., Tran, B.V., and Huntsman, M.M. Nucleus- and cell-specific expression of NMDA and non-NMDA receptor subunits in monkey thalamus. Journal of Comparative Neurology 397:371-393, 1998.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000169-38
Application #
6116632
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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