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. 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 somatosensory synaptic circuitry is altered following impaired NMDAR function. In vivo and in vitro electrophysiological approaches will be used to elucidate functional changes in the somatosensory cortex and thalamus of these mice. These studies will complement ongoing morphological analyses and overall reveal the role of NMDARs in organization and patterning of somatosensory neural maps.

Public Health Relevance

NMDA receptors (NMDARs) play a major role in brain development, learning and memory, developmental neurological disorders, addiction, pain perception and in excitotoxicity. In this proposal we shall test the role of NMDARs in normal development of somatosensory neural circuits by examining physiological defects in region-specific genetic invalidation of NMDARs in mouse models. Understanding basic cellular and molecular mechanisms of NMDAR function in normal brain development is crucial for critical evaluation of developmental brain disorders and in developing therapeutic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS039050-11S1A1
Application #
8102609
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
2011-04-01
Budget End
2011-12-31
Support Year
11
Fiscal Year
2011
Total Cost
$328,125
Indirect Cost
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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