TRIGEMINOTHALAMIC ORGANIZATION AND PLASTICITY

三叉丘脑组织和可塑性

• 批准号: 3222819
• 负责人: NICOLAS Louis CHIAIA
• 金额: $ 8.88万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-03-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3222819
• 关键词: afferent nerve; brain stem; central neural pathway /tract; developmental neurobiology; electrophysiology; embryo /fetus; evoked potentials; ganglion cell; horseradish peroxidase; implant; intracellular; laboratory rat; microelectrodes; neural plasticity; neuroanatomy; neurogenesis; neurons; neurophysiology; newborn animals; penicillins; tetrodotoxin; thalamus; trigeminal nerve

Our aim is to understand the mechanisms operating during pattern formation in the trigeminal (V) system. One mechanism thought to be important in this process is neuronal activity. However, recent experiments funded by this grant showed that blockade of cortical activity has no appreciable effect upon normal thalamocortical pattern formation. In view of previous findings from other systems, these results are quite surprising. The aim of the studies proposed in this renewal application is to determine the reason for this apparent difference between the conditions necessary for the normal development of the rat's V neuraxis and neuronal connections in many portions of the brains of this and other species. Our working hypothesis is that neuronal activity plays little role in V pattern formation in the rat because the normal ontogeny of this system occurs when activity levels are very low and thus incapable of influencing refinement of projections. It therefore follows that abnormally increased activity should alter V thalamocortical development and that normal activity may play a substantial role in the refinement of V cortico-cortical connections which develop at postnatal ages when levels of patterned activity are considerably higher. We will carry out four types of experiments to test this hypothesis: 1) We will directly assess levels and patterns of neuronal activity in the developing V system by recording from V ganglion cells and from neurons in V nucleus principalis (PrV), the ventral posteromedial thalamus (VPM), and primary somatosensory cortex (S-1) in unanesthetized in vivo preparations. With the exception of limited data from anesthetized animals and a small number of in vitro studies, we have no information that addresses this question in any portion of the developing V system. 2) We will employ intracellular recording from in vitro preparations to determine the ages at which ascending functional connections are made at each level of the V neuraxis. 3) We will interfere with activity in the developing V system by induction of abnormal patterns rather than blockade. We will create foci of abnormal activity by placement of penicillin-impregnated, slow-release polymer implants in the developing cortex. If activity is capable of modifying pattern formation, the experimental induction of foci of high and correlated activity should alter thalamocortical development. 4) We will assess the effects of activity blockade upon the development of cortico-cortical pathways that mature postnatally when levels of patterned activity in the developing cortex more closely approximate those observed in adult animals. Here, TTX implants will be used to silence cortex, and development of the callosal and associational projections of the primary somatosensory cortex will be evaluated using both anterograde and retrograde tracing techniques.

我们的目的是了解在模式期间的运作机制 在三叉神经（V）系统中形成。一种机制被认为是 在这个过程中重要的是神经元活动。 但最近的 由该基金资助的实验表明， 活动对正常的丘脑皮质模式没有明显的影响 阵 鉴于其他系统的先前发现，这些 结果是相当令人惊讶的。 本文提出的研究目的是 更新申请是为了确定这一明显的原因 正常发展所必需的条件之间的差异 大鼠的V神经轴和神经元连接的许多部分， 这个物种和其他物种的大脑。 我们的假设是 神经元活动在大鼠V型形成中的作用不大 因为这个系统的正常个体发育发生在活动水平 非常低，因此不能影响预测的细化。 因此，活动异常增加应改变V 丘脑皮质发育和正常活动可能起着重要作用， 在完善V皮质-皮质连接中的实质性作用 在出生后的年龄，当模式化的活动水平， 相当高。 我们将进行四类实验来检验 这一假设：1）我们将直接评估的水平和模式， 通过从V神经节记录发育中的V系统的神经元活动 细胞和神经元的V主核（PrV），腹侧 后内侧丘脑（VPM）和初级躯体感觉皮层（S-1）， 未麻醉的体内制剂。 除了有限的数据 从麻醉的动物和少量的体外研究中， 没有任何信息，解决这个问题的任何部分， 开发V系统。2)我们将采用细胞内记录， 体外制剂，以确定上升功能的年龄， 在V神经轴的每一个水平都有连接。3)我们将 通过诱导干扰发育中的V系统的活性 异常模式而不是阻塞。 我们会在你的大脑中 通过放置青霉素浸渍的缓释聚合物的活性 植入发育中的皮层 如果活动能够修改 模式形成，实验诱导高和 相关的活动应该会改变丘脑皮层的发育。4)我们将 评估活动封锁对发展的影响， 皮质-皮质通路在出生后成熟， 发育中的皮质中的模式活动更接近 在成年动物中观察到的。 在这里，TTX植入物将用于 沉默皮层，以及胼胝体和联合的发育 初级躯体感觉皮层的投射将使用 顺行和逆行追踪技术。