DEVELOPMENT OF SPECIFIC NEURONAL CONNECTIONS IN LEECH

改编自申请人摘要的描述)：准确的组织 单个神经元进入神经回路对所有神经来说都是必不可少的 功能。越来越多的证据表明，这种令人衰弱的精神 精神分裂症和自闭症等疾病可能是由神经功能衰竭引起的 电路才能正常发育。神经电路的一个共同特征是 将多个输入汇聚到一个目标上。这种融合 要求神经元不仅找到并与适当的 突触后细胞，但也适当地与其他 投入。在某些情况下，电路的功能关键取决于 突触前细胞与特定的亚区的精确连接 突触后神经元，例如，在单个树突分支上或在 轴突的起始段。简单地研究这一发展 神经系统不仅可以让人了解相关的机制，而且 也可能最终使人能够解释 不适当的开发。拟议中的实验旨在 描述一组神经元子集之间的联系 药用水蛭的特殊行为，局部弯曲反射。 具体地说，来自两对兴奋性神经的连接 将研究将中间神经元连接到共享的突触后运动神经元。这个 每个连接的准确位置将通过光消融来识别 分支和随后的细胞内电记录 突触前和突触后细胞。第一次连接的时间 显影将通过使用成对的电子记录在几个 不同的胚胎年龄。最后，相互作用的作用 突触前神经元，以及突触前神经元之间的特异性 在产生精确连接的过程中，突触后分支将被评估 通过消融整个突触前细胞或个别突触后分支 在开发过程中，在建立任何连接之前。

DESCRIPTION Adapted from applicant's abstract): The precise organization of individual neurons into neural circuits is essential for all neural functions. There is increasing evidence that such debilitating mental diseases as schizophrenia and autism may result from failure of neural circuits to develop properly. A common feature of neural circuits is the convergence of several inputs onto a single target. This convergence requires that a neuron not only find and synapse with the proper postsynaptic cell, but also appropriately share this target cell with other inputs. In some cases, the functioning of the circuit critically depends on the precise connection of the presynaptic cell onto a specific sub-region of the postsynaptic neuron, for example, onto a single dendritic branch or onto the initial segment of the axon. Studying this development in a simple nervous system not only allows one to learn the mechanisms involved, but also may eventually allow one to interpret the functional consequences of inappropriate development. The experiments proposed are designed to characterize the connection between a subset of neurons involved in a specific behavior, the local bending reflex, in the medicinal leech. Specifically, the connection from each of two pairs of excitatory interneurons onto a shared postsynaptic motor neuron will be studied. The precise location of each connection will be identified by photoablation of branches and subsequent intracellular electrical recording of the presynaptic and postsynaptic cells. The time at which the connection first develops will be determined by using paired electrical recordings at several different embryonic ages. Finally, the role of interactions among presynaptic neurons, as well as between the presynaptic neuron with specific postsynaptic branches, in generating precise connections, will be assessed by ablating entire presynaptic cells or individual postsynaptic branches during development, before any connections are made.