2-DEOXYGLUCOSE STUDIES OF THE WHISKER-BARREL NEURAXIS

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DESCRIPTION: The principal investigator's objective is to use neurobehavioral and high-resolution 2-DG mapping tools to determine: 1) the neural mechanisms responsible for activation of CNS somatosensory structures, 2) when and how these activation patterns develop, 3) if experiential factors control the emergence of these activation patterns in development and their maintenance in adulthood, and 4) if experience- dependent plasticity is more robust when the system is deprived prior to or after the emergence of these activation patterns in development. Thus, proposed studies will uncover mechanisms responsible for the sense of touch and its "state-dependent" modulation, development and plasticity. The mouse whisker-to-barrel neuraxis has advantages over other systems for addressing these issues; namely, a readily visualized and stringent point-to-point topography, digitized and lever-like receptor organs for quantitative stimulus control, established pathways and circuits, and precise rules governing its development. Yet, there are inconsistencies in the literature regarding those portions of the barrel neuraxis that are activated by whisker deflection, when assayed by 2DG uptake. The principal investigator's view of these "discrepancies" is that they reflect instructive differences in the way whiskers were deflected to evoke 2DG uptake. Site- and behavioral task- related variables appear to interact to affect levels and patterns of neuronal activity evoked by whisker deflections. The principal investigator proposes to assess whether 2DG uptake patterns differ when single whiskers are displaced "actively" or passively", whether such differences predict the functions of "lemniscal" and "paralemniscal" pathways, and whether corticofugal pathways and whisking behavior impact on 2DG uptake patterns during "active" and "passive" touch. Developmental studies are also offered to determine whether prior indications of weak or absent single-unit responses to whisker stimuli in immature rats reflect less than ideal physiological recording conditions. Proposed 2DG mapping, on the other hand, marks active compartments of single cells in behaving animals without anesthesia. An identical series of experiments to those proposed for adult mice will be performed at various times in development. The principal investigator predicts that prior to development of whisking behavior (up to about 2 weeks of age), animal- and experimenter-initiated displacements of single whiskers will produce equally robust 2DG uptake in all subcortical lemniscal and paralemniscal sites receiving inputs from the stimulated whisker, unlike the labeling patterns seen in normal adults. He also predicts that whisker deprivation from birth will preserve the immature pattern of whisker-evoked 2DG uptake, that the "critical period" for such plasticity extends up to the age when whisking first appears, and that deprivation-induced changes are irreversible. He also predicts that whisker deprivation in adulthood leads to a use-dependent disengagement of cortical modulation of whisker-evoked 2DG uptake, and that deprivation-induced changes in mature animals are reversible. The applicant team has experience with the methods necessary to resolve these issues and a record of effective collaboration. These studies will uncover general rules governing somatosensation in humans because of recent indications that primates have barrel-like cell and fiber aggregations in somatosensory nuclei.