The long term objectives of this proposal are to understand the cellular and molecular mechanisms that underlie the capacity of the cerebral cortex to adapt to changes in patterns of input from the peripheral sense organs in adults. These mechanisms probably not only play a role in the fundamental processes involved in the learning of skills and the capacity to make perceptive judgements about the external world but also appear to be involved in the aberrant perceptions that accompany perturbed peripheral sensory input, for example in the case of pain of central nervous origin. The proposed studies, to be carried out in macaque monkeys, involve deprivation of sensory input from the hand and arm by peripheral nerve section or reversible conduction block, and enhanced input by electrical stimulation, the induction of acute arthritis or innocuous tactile, self-stimulation. The hand representation of the first somatosensory area of the cerebral cortex (SI) will be examined by immunocytochemical, receptor binding and in situ hybridization histochemistry to detect changes in gene expression for molecules that form the components of the gamma aminobutyric acid (GABA) and glutamate containing neuronal systems of the cortex. Changes in the representation pattern in Sl that accompany these will be mapped by multiunit recording. The effects of activity-dependent, up-or down-regulation of transmitter related molecules will be assayed by single unit/iontophoretic studies GABA and glutamate agonists and antagonists. A potential underlying basis of activity dependent plasticity, in widespread intracortical terminations of single thalamocortical axons, will be examined in correlative neuroanatomical tracing studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS021377-08
Application #
3402466
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1984-08-01
Project End
1995-08-31
Budget Start
1991-09-03
Budget End
1992-08-31
Support Year
8
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Type
Schools of Medicine
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Liu, Xiao-Bo; Murray, Karl D; Jones, Edward G (2011) Low-threshold calcium channel subunit Ca(v) 3.3 is specifically localized in GABAergic neurons of rodent thalamus and cerebral cortex. J Comp Neurol 519:1181-95
Jones, Edward G (2009) Synchrony in the interconnected circuitry of the thalamus and cerebral cortex. Ann N Y Acad Sci 1157:10-23
Graziano, Alessandro; Jones, Edward G (2009) Early withdrawal of axons from higher centers in response to peripheral somatosensory denervation. J Neurosci 29:3738-48
Mikula, Shawn; Manger, Paul R; Jones, Edward G (2008) The thalamus of the monotremes: cyto- and myeloarchitecture and chemical neuroanatomy. Philos Trans R Soc Lond B Biol Sci 363:2415-40
Murray, Karl D; Rubin, Carol M; Jones, Edward G et al. (2008) Molecular correlates of laminar differences in the macaque dorsal lateral geniculate nucleus. J Neurosci 28:12010-22
Graziano, Alessandro; Liu, Xiao-Bo; Murray, Karl D et al. (2008) Vesicular glutamate transporters define two sets of glutamatergic afferents to the somatosensory thalamus and two thalamocortical projections in the mouse. J Comp Neurol 507:1258-76
Liu, Xiao-Bo; Coble, Jeffrey; van Luijtelaar, Gilles et al. (2007) Reticular nucleus-specific changes in alpha3 subunit protein at GABA synapses in genetically epilepsy-prone rats. Proc Natl Acad Sci U S A 104:12512-7
Murray, Karl D; Choudary, Prabhakara V; Jones, Edward G (2007) Nucleus- and cell-specific gene expression in monkey thalamus. Proc Natl Acad Sci U S A 104:1989-94
Graziano, Alessandro; Jones, Edward G (2004) Widespread thalamic terminations of fibers arising in the superficial medullary dorsal horn of monkeys and their relation to calbindin immunoreactivity. J Neurosci 24:248-56
Liu, Xiao-Bo; Murray, Karl D; Jones, Edward G (2004) Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development. J Neurosci 24:8885-95

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