FUNCTIONAL RECOVERY FOLLOWING NEURAL INJURY IN EMBRYOS

对于基础和临床神经科学来说，一个重要的问题是为什么 发育中的神经系统似乎更有能力进行功能修复， 比成年人的伤害更大。一个相关的问题是，成年神经元是否可以 从伤害中恢复使用的机制，成功地采用了发展 神经元尽管在这一领域进行了大量的研究，但很少有研究分析 单个神经元在发育期与成年期的反应 动物在解剖、生理和行为恢复方面 受伤后的功能。在水蛭的相对简单的神经 系统，不仅可以研究行为，它的调制和 潜在的神经回路，而且离散病变的影响， 个人联系和行为。此外，许多神经元 在胚胎发生早期就可以识别，从而可以研究 在正常和正常的神经元和它们的连接中， 受伤的胚胎该提议集中在神经元中的单个中间神经元。 水蛭，S细胞，在成年动物中， 典型的时尚。此外，S细胞已被证明是 对感觉运动反射的正常非联想学习至关重要 （缩短）即使它不是自反行为所必需的， 只是为了它的修改。杀死S细胞的胚胎损伤导致 形成至少一个异常连接，恢复一些正常的 生理功能本提案测试中概述的实验 关于胚胎发育所用细胞机制的具体假设 神经元形成非典型连接的能力以及这些连接的能力 来支持非联想学习此外，非典型的稳定性 在发育过程中形成的连接可以在成年后进行分析。 实验方法包括解剖学、生理学和行为学 技术组合以表征S细胞突触连接， 损伤后形成的非典型连接及其与 非联想学习这些实验将提供深入了解 神经系统发育的细胞机制 对损伤的补偿反应以及胚胎和成人的机制 来恢复复杂的行为。

A question important to basic and clinical neuroscience is why the developing nervous system seems more capable of functional repair after injury than the adult. A related question is whether adult neurons can recover from injury using-mechanisms successfully employed by developing neurons. Despite intense research in this area, few studies have analyzed the response of single identified neurons in developing versus adult animals with regard to anatomical, physiological and behavioral recovery of function following injury. In the leech's relatively simple nervous system it is possible to study not only behavior, its modulation and the underlying neuronal circuit, but also the effects of discrete lesions on individual connections and behavior. In addition, many neurons are identifiable early in embryogenesis, allowing investigations into the development of individual.neurons and their connections both in normal and injured embryos. This proposal is focussed on a single interneuron in the leech, the S cell, which in adult animals responds to injury in a characteristic fashion. In addition, the S cell has been shown to be essential to normal nonassociative learning of a sensory-motor reflex (shortening) even though it is not required for the reflexive behavior but only for its modification. Embryonic lesions that kill an S cell cause the formation of at least one aberrant connections that restores some normal physiological functioning. Experiments outlined in this proposal test specific hypothesis concerning the cellular mechanisms used by embryonic neurons to form atypical connections and the ability of these connections to support nonassociative learning. In addition, the stability of atypical connections formed during development can be analyzed later in adulthood. Experimental methods include anatomical, physiological and behavioral techniques in combination to characterize S cell synaptic connections, atypical connections formed following injury and their link to nonassociative learning. These experiments will provide insights into cellular mechanisms underlying the developing nervous system's compensatory response to injury and into mechanisms in embryos and adults for the recovery of complex behavior.