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, and in adaptation to central and peripheral nervous injury. The proposed studies, to be carried out in macaque monkeys, involve three principal sets of. experiments. The first set deals with how converging and diverging connections extending from the -thalamus to the somatosensory cortex may facilitate plasticity of representations of the body, but -place constraints upon the extent to which changes can occur. The second set of experiments deals with the issue of whether pre-existing connections within the somatosensory cortex itself are sufficient to permit large scale changes in representational maps after long-term deafferentation or whether it is necessary for new connections to be formed. This set introduces a new model for the studies of cortical plasticity, the face representation, and addresses the issue of whether it is protected"""""""" from other parts of the somatosensory cortex by an absence of interconnections. The third set of experiments deals with the normal patterns of gene expression for receptor subunits and other polypeptides that form components of the inhibitory (GABAergic) and excitatory (glutamergic) transmitter systems of the cerebral cortex and thalamus and asks to what extent activity-dependent changes in gene expression for these molecules accompany and/or contribute to representational plasticity. The methods are a combination of anatomical tracing, physiological mapping in normal animals and in animals in which part of the thalamic representation has been selectively lesioned, coupled with immunocytochemistry and in situ hybridization histochemistry, and including a search for novel GABA-A receptor subunit genes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021377-14
Application #
2460504
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Broman, Sarah H
Project Start
1984-08-01
Project End
1998-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
14
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
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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