Plasticity in Unitary Synaptic Connections

描述（由申请人提供）：Synaptic塑料工艺，如 长时程增强（LTP）和长时程抑制（LTD）在脑电活动中起着重要作用 在几乎所有试图解释细胞学习和记忆的模型中， 水平除此之外，LTP和LTD还存在于许多大脑区域， 被认为在广泛的神经功能和疾病中发挥作用。 神经功能从恐惧和情感，通过记忆成瘾已经被 建议在这些塑料工艺中建立基础。因此 了解这种可塑性的机制将提供 广泛的好处不仅是了解正常的大脑功能， 许多神经系统疾病的症状LTP和LTD的研究一直受到 相互矛盾的理论和实验结果，在许多情况下， 在理解这些神经元的潜在机制方面的进展 特性.我们认为，这种混乱主要是由于技术原因造成的。 实验的局限性，必然，完全依赖于 在大量突触中测量突触可塑性。以来 可以发现突触处于各种可塑性状态，例如幼稚的，增强的， 突触的数量几乎肯定包含所有这些 国家和更多，实验操作可能会提供混乱的结果。多 如膜片钳记录，其中少量离子通道的活性 可以单独记录，彻底改变了离子通道的研究 功能突触可塑性领域可以从实验中受益， 可以选择性地研究和操纵非常少量的突触。在 在这个建议中，我们采用了一种方法，我们可以记录小的活动， 许多突触（1-10）识别它们的可塑性状态， 操纵这个国家。通过这样做，我们可以研究 在我们知道突触历史的情况下， 正在研究中。在我们的初步研究中，我们已经澄清了几个 与突触可塑性机制有关的问题，并期望 这项建议的实验将大大扩展我们对这些问题的认识。 机制等

DESCRIPTION (provided by applicant): Synaptic plastic processes such as long-term potentiation (LTP) and long-term depression (LTD) play a central role in virtually all models that seek to explain learning and memory at a cellular level. Beyond even that, LTP and LTD are found in many brain areas and have been proposed to play a role in a wide range of neural functions and disorders. Neural functions from fear and emotion, through memory to addiction have been proposed to have a basis in these plastic processes. Therefore, the understanding of the mechanisms that underlie this plasticity will provide wide-ranging benefits not only to understanding normal brain function, but also to many neurological disorders. The study of LTP and LTD have been plagued by conflicting theories and experimental results that has in many cases slowed progress in understanding the underlying mechanism of these neuronal properties. Much of this confusion, we believe, has arisen from technical limitations of experiments that have, by necessity, relied exclusively on measures of synaptic plasticity in large populations of synapses. Since synapses can be found in a variety of plastic states, e.g. naive, potentiated, depressed, and populations of synapses almost certainly contain all these states and more, experimental manipulations may provide confusing results. Much as patch clamp recording, where the activity of a small number of ion channels could be recorded in isolation, revolutionized the study of ion channel function. the field of synaptic plasticity could benefit from experiments where very small numbers of synapses could be selectively studied and manipulated. In this proposal, we employ a method where we can record the activity of small numbers of synapses (1-10) identify their plastic state, and experimentally manipulate that state. By doing so, we can study the transitions between different plastic states in cases where we know the history of the synapses under study. In our preliminary studies, we have already clarified several issues relating to the mechanisms of synaptic plasticity and expect that the experiments in this proposal will greatly expand our knowledge of these mechanisms.