2-DEOXYGLUCOSE STUDIES OF THE WHISKER-BARREL NEURAXIS

描述：主要研究者的目的是使用 神经行为和高分辨率2-DG绘图工具，以确定：1） 负责激活CNS躯体感觉的神经机制 结构，2）这些激活模式何时以及如何发展，3）如果 经验因素控制着这些激活模式的出现 在发展和他们的维护在成年，和4）如果经验- 当系统被剥夺先验时，依赖塑性更鲁棒 在这些激活模式出现之前或之后。 因此，拟议的研究将揭示负责感觉的机制， 触摸及其“状态依赖”调制，发展和 可塑性。 小鼠须-桶神经轴优于 解决这些问题的其他系统;即， 和严格的点对点地形，数字化和数字化 定量刺激控制的受体器官，已建立的途径 和电路，以及控制其发展的精确规则。 然而， 是文献中关于这些部分的不一致之处， 当测定时， 2DG的吸收。 首席研究员对这些问题的看法 “差异”是指它们反映了 使晶须偏转以引起2DG摄取。 地点-和行为任务- 相关变量似乎相互作用，影响水平和模式， 由胡须偏转引起的神经元活动。 校长 研究者建议评估2DG摄取模式是否不同， 单根晶须被“主动”或“被动”地移位， 差异预测“丘系”和“双丘系”的功能 通路，以及离皮质通路和搅拌行为是否影响 在“主动”和“被动”触摸期间的2DG摄取模式。 还提供了发育研究，以确定先前是否 对触须刺激的单一单位反应弱或缺失的迹象 在未成年大鼠中反映出不太理想的生理记录 条件 另一方面，拟议的2DG映射标志着活跃的 在没有麻醉的行为动物中的单个细胞的隔室。 一系列与成年小鼠相同的实验将 在开发过程中的不同时间执行。 校长 研究人员预测，在搅拌行为发展之前（向上）， 至约2周龄），动物和实验者引发的 单根晶须的位移将产生同样强劲的2DG吸收 在所有接受输入的皮层下丘系和丘系部位 从刺激的胡须，不像在正常的标记模式， 成年人了 他还预测，从出生起胡须就被剥夺， 保留胡须诱发的2DG摄取的不成熟模式， 这种可塑性的“关键期”一直延续到 搅拌首先出现，而剥夺引起的变化是 不可逆的 他还预测，成年后的胡须缺失 导致皮层调制的使用依赖性脱离， 胡须引起的2DG摄取，以及剥夺引起的 成熟的动物是可逆的。 申请人团队具有以下经验： 解决这些问题所需的方法和有效的记录 协作 这些研究将揭示 人类的躯体感觉，因为最近的迹象表明， 在躯体感觉核团中有桶状细胞和纤维聚集。

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.