2-DEOXYGLUCOSE STUDIES OF THE WHISKER-BARREL NEURAXIS

描述：首席调查员的目标是使用 神经行为和高分辨率2-DG测绘工具，以确定：1) 中枢神经系统躯体感觉激活的神经机制 结构，2)何时以及如何发展这些激活模式，3)如果 经验因素控制着这些激活模式的出现 在发育和成年后的维持，以及4)如果经验- 当系统事先被剥夺时，依赖可塑性更稳健 在发育过程中出现这些激活模式之前或之后。 因此，拟议中的研究将揭示导致这种感觉的机制 触觉及其“状态依赖”的调制、发展和 可塑性。小鼠胡须到管状神经轴的优势超过 用于解决这些问题的其他系统；即，易于可视化的 和严格的点对点地形，数字化和杠杆式 数量刺激控制的受体器官，已建立的途径 和电路，以及指导其发展的精确规则。然而，在那里 文献中关于这些部分的不一致之处 检测时因胡须偏转而激活的桶状神经轴 通过2DG摄取。首席调查员对这些问题的看法 “差异”是因为它们反映了不同的方式 胡须被偏转以引起2DG摄取。现场和行为任务- 相关变量似乎相互作用，以影响水平和模式 胡须偏转引起的神经元活动。校长 研究人员建议评估2DG摄取模式是否在以下情况下有所不同 单一的晶须被“主动”或“被动”地置换，无论是这样 “Lemniscal”和“Paralniscal”功能的差异预测 途径，以及皮质醇途径和甩动行为是否影响 “主动”和“被动”触摸过程中2DG摄取模式的研究 发展研究也被用来确定之前 对胡须刺激的单一单位反应微弱或不存在的迹象 在未成熟的大鼠身上反映出不太理想的生理记录 条件。另一方面，建议的2DG映射标记为活动的 在没有麻醉的情况下，行为动物的单细胞隔间。 一系列与建议用于成年小鼠的实验相同的实验将 在发育的不同时期进行。校长 研究人员预测，在发展搅拌行为(UP)之前 到大约2周大)，由动物和实验者发起 单个晶须的位移将产生同样强劲的2DG吸收 在接受输入的所有皮质下丘疹和丘脑旁部位 从受刺激的胡须，不同于正常情况下看到的标记模式 成年人。他还预测，从出生起就被剥夺的胡须将 保留胡须引发的2DG摄取的未成熟模式，即 这种塑性的“关键期”一直延伸到 搅拌最先出现，而剥夺诱导的变化是 不可逆转。他还预测，成年后胡须的缺失 导致依赖于使用的大脑皮质调制的脱离 晶须诱发的2DG摄取，以及剥夺诱导的变化 成熟的动物是可逆的。申请者团队具有以下经验 解决这些问题所需的方法和有效的记录 协作。这些研究将揭示出 人类的躯体感觉，因为最近有迹象表明灵长类 体感核内有桶状的细胞和纤维聚集。

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.