TRIGEMINOTHALAMIC ORGANIZATION AND PLASTICITY

我们的目标是了解模式运行的机制 三叉神经(V)系统的形成。有一种机制被认为是 在这个过程中，重要的是神经元的活动。然而，最近 由这笔赠款资助的实验表明，大脑皮质的阻断 活动对正常丘脑皮质模式没有明显影响 队形。鉴于以前来自其他系统的调查结果，这些 结果相当令人惊讶。本报告中提出的研究目的是 续签申请是为了确定出现这种情况的原因 正常发展所需的条件之间的差异 大鼠V型神经轴和丘脑多节区的神经元联系 这个物种和其他物种的大脑。我们的工作假设是 神经元活动在大鼠V型波形成中的作用不大 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精细化。 因此，异常增加的活动量应该改变V 丘脑皮质发育和正常活动可能起到 在改进V形皮质-皮质连接中的重要作用 在出生后的年龄，当模式化的活动水平是 要高得多。我们将进行四种类型的实验来测试 这一假设：1)我们将直接评估 从V神经节记录发育中的V系统的神经元活动 腹侧V主核(PRV)的细胞和神经元 后内侧丘脑(VPM)和初级体感皮层(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，我们有 中的任何部分都没有解决此问题的信息 发展V系统。2)我们将从In使用细胞内记录 体外制剂，以确定上升功能的年龄 在V神经轴的每个水平上都有联系。3)我们会 通过诱导干扰发育中的V系统的活动 反常模式，而不是封锁。我们将创建异常的焦点 通过放置青霉素浸渍的缓释聚合物的活性 植入发育中的皮质。如果活动能够修改 花纹形成，高位和高位病灶的实验性诱导 相关的活动应该会改变丘脑皮质的发育。4)我们会 评估活动封锁对发展的影响 皮质-皮质通路在出生后成熟时水平 发育中皮质中的模式活动更接近于 在成年动物身上观察到的那些。在这里，TTX植入物将被用于 无声皮质与胼胝体和联合体的发育 初级躯体感觉皮质的投射将使用 顺行和逆行追踪技术。

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.