Neurons in somatic sensory cortex receive sensory information from the periphery throughout postnatal life. The central hypothesis for the proposed studies is that simple positive biases in the level of ongoing activity from selected whiskers is enough to potentiate their targeted synapses in cortex through glutamate receptor mechansisms. The studies will be carried out in the rat whisker to barrel field cortex pathway because the discrete, non-overlapping receptors in each whisker follide maintain a dear topography to and induding layer Iv of barrel field cortex. In addition, we have demonstrated that the receptive fields of neurons in adult rat barrel field cortex are modified by simply trimming some, but not all, of the whiskers for periods as short as 1 day or up to 30 days. Trimming all but two adjacent whiskers significantly increased the response of cortical neurons to spared whiskers and dramatically diminished the response to cut whiskers. The changes induced by whisker pairing were multifaceted and depend upon cell location in the barrel field cortex, the barrel's relationship to each whisker in the receptive field and how long they were trimmed or spared.
Four specific aims are identified to analyze the circuits and mechanisms that support these plastic responses in adult rat cortex:
Aim #1 is to compare the rate of change of synapses in each cortical layer induced by whisker pairing. Preliminary results show that supragranular neurons change before cells in any other layer. Two specific sub-goals are to test whether whisker pairing plasticity in the deeper layers requires prior changes in the superficial layers of cortex and whether the plasticity depends on glutamate receptor mechanisms.
Aim #2 is to compare the limits of response enhancement that can be generated in the VPM thalamocortical fiber synapses before and after whisker pairing.
Aim #3 is to analyze the role of extraIemniscal sensory modulators to barrel field cortex in the spread of activity between non-adjacent barrels when induced by whisker pairing. We will trim all but two non-adjacent whiskers to determine the effect of SII and POm lesions on the distance-limit for modifying connections between cortical barrels of the two intact whiskers.
Aim #4 is to show the effect of depletion of non-sensory neuromodulators in cortex on whisker pairing plasticity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Special Emphasis Panel (ZRG1-IFCN-4 (03))
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Michel, Mary E
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Vanderbilt University Medical Center
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