The role of neural activity in wiring and plasticity of sensory pathways is a major topic of interest in developmental neuroscience. A vast body of literature underscores the importance of N-methyl D Aspartate (NMDA) receptor- mediated neural activity during development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system. This proposal focuses on the development of somatosensory thalamocortical circuitry in mice with genetically impaired NMDAR function. Rodent somatosensory pathway is an excellent model system to study development of topographic connections and patterning within somatosensory maps. Somatosensory patterns are abolished in the brainstem of mice lacking the critical subunit of the NMDARs. Mice that express lower levels of NMDAR function also show absence of patterning all along the somatosensory pathway. Mice with cortex-restricted disruption of NMDARs in excitatory neurons also display severe defects in cortical patterning within the somatosensory body map region. Aside from axonal and postsynaptic defects, the subdivisions of the somatosensory body map within the neocortex are altered. Thus, somatosensory region-specific knockout mouse models provide an excellent means to dissect out the role of NMDARs and downstream signaling molecules in patterning of pre- and postsynaptic neural elements. The long-term objective of this proposal is to reveal how axon arbors and dendritic processes of postsynaptic cells are altered following impaired NMDAR function. Combined molecular genetic and neuroanatomical approaches will be used to elucidate structural changes in the somatosensory cortex and thalamus of these mice. A clear understanding of such anatomical changes will pave the way for dissecting out molecular mechanisms of pattern formation and plasticity in developing mammalian sensory pathways. These studies could then be expanded to investigate mechanisms of adult cortical plasticity during learning or as a consequence of peripheral nerve damage.

Public Health Relevance

N-methyl D Aspartate (NMDA) receptors (NMDARs) play a major role in development of neural connections and their plasticity, learning and memory, as well as during excitotoxicity in pathological states of the mature nervous system. In this proposal we shall test the role of NMDARs in the development and plasticity of somatosensory neural circuits by examining neural defects in NMDAR-deficient mouse models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS039050-12
Application #
8209176
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Riddle, Robert D
Project Start
2000-04-01
Project End
2013-12-31
Budget Start
2012-01-01
Budget End
2012-12-31
Support Year
12
Fiscal Year
2012
Total Cost
$584,063
Indirect Cost
$194,688
Name
University of Maryland Baltimore
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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