Functional Segregation Within the Whisker-Barrel Neuraxis

晶须桶神经轴内的功能分离

基本信息

批准号：
10424659
负责人：
Mitra J Hartmann
金额：
$ 10.67万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10424659
关键词：
Functional Segregation Within Whisker Barrel

项目摘要

DESCRIPTION (provided by applicant): The long-term objectives of this multi-PI R01 proposal are two-fold. First, the functions of specific parallel neural pathways (lemniscal, paralemniscal) linking brainstem and forebrain trigeminal (V) representations will be revealed. This will be done in the rodent whisker-to-barrel cortex neuraxis, which has become the model of choice for discovery of information processing mechanisms, due to the prominence of barrels in the cerebral cortex of transgenic mice. Yet, there are major gaps in our knowledge of subcortical components that hamper our grasp of the whisker-barrel circuit. These gaps will be filled by applying a set of multidisciplinary tools to studies of the neural control of whisker-related sensation and movement. Our overarching hypothesis is that neural activity in the spinal V subnucleus interpolaris (SpVi, paralemniscal) is necessary for whisker-mediated object detection and orientation responses, while whisker-mediated object identification and discrimination require neural activity in a topographically patterned (barrelettes) V nucleus principalis (PrV, lemniscal). Three Specific Aims employ: a) transgenic mice that lack barrelettes in PrV, but not in SpVi, b) reversible allatostatin- induced silencing of adenovirus transduced multi-whisker responsive SpVi cells or single-whisker PrV cells, and c) anatomical and electrophysiological assessments of the integrity and neurotransmission properties of V brainstem neurons in animals studied in the above 2 Aims. Thus, "gene deletion" and "neural silencing" approaches are coupled with parallel validation of the extent to which these 2 approaches produce "functional lesions" in V brainstem neurons. This permits discovery of components of the barrel neuraxis that are unequivocally responsible for whisker-mediated detection, orientation, identification and discrimination behaviors. Second, this research will als provide technical 'proof of principle' for the potential use of above- listed allatostatin-induced silencing of adenovirus infected neurons to treat human neurological disorders, such as epilepsy, chronic pain, obesity and addiction, where hyperexcitability characterizes defined neuronal populations, reduction or elimination of which could constitute a new treatment strategy. Self-administration of allatostatin could be a transformative treatment option, the efficacy of which will be evaluated here in a simple model system, with an eye towards possible side effects. A collaborative venture is offered with 3 PIs that are indispensable to the accomplishment of all 3 Specific Aims. Dr. Zeigler developed the "head-fixed" technology required to deliver stimuli to single whiskers, to monitor their movements and to bring such movements under voluntary control. These tools will be used in Aims 1 and 2. Dr. Hartmann developed the "head-free" technology required to measure and control movements of single whiskers, as well as means to analyze video materials of such. These tools will be used in Aims 1 and 2. Dr. Jacquin's career has been largely devoted to the trigeminal system and brings expertise on transgenic mice, allatostatin/adenoviruses and single unit recording to bear upon the behavioral issues and technology offered here by Drs. Hartmann and Zeigler.

描述（由申请人提供）：多PI R01提案的长期目标是两倍（Leansiscal，lemansiscal，saralesslemanscal），将脑干和前脑三叉戟（V）抑制作用。晶须至桶皮层神经，这已成为门徒机械SMS的首选模型，这是由于转基因小鼠的大脑皮层的突出性，但我们对亚皮质组成部分的知识存在重大差距。时间限制工具，用于研究与晶须相关的感觉和运动的神经控制。（PRV，Lemniscal）。通过平行验证这两种方法在脑干神经元中产生“功能性病变”的程度。识别和歧视行为。这项研究意愿为上述allatostatin的潜在SE提供技术“原理”，以对脑干神经元中的“功能性病变”进行平行验证。 - 腺病毒的沉默治疗人类神经病学障碍，例如癫痫病，肥胖症D，在该疾病中，过度的神经元普及了allatostatin的自我管理。为了实现所有三个特定目标，Zeigler博士开发了在自愿控制下向单个晶须提供刺激所需的技术。在目标1和2中，Jacquin博士在很大程度上专门用于三叉神经系统，并为转基因小鼠，allatostatin/adenoviruse和单个单位记录带来了专业知识。