Homosynaptic Long-Term Depression: Mechanisms and Role in Learning

LAY ABSTRACT IBN-9808930 大多数神经科学家认为，大脑中神经元之间的连接（突触）强度的变化是学习和记忆的基础。大脑中的突触可能会增加强度，或减少强度，作为动物学习的结果。发生在哺乳动物大脑中的突触强度变化的一种突出形式被称为同突触长期抑制或LTD。LTD是突触强度的降低，持续60分钟至数小时，由突触前神经通路的低频刺激产生。由于海马体在哺乳动物的学习和记忆中起着重要作用，因此LTD被认为可能代表了记忆的神经机制。 然而，尽管对海马中LTD的研究已经进行了五年，但对LTD的细胞机制了解甚少。此外，关于海马突触的LTD在学习和记忆中可能发挥的作用，了解得更少。 部分困难在于海马体是一个复杂的结构。 此外，涉及海马体的学习类型在神经生物学水平上很难理解。 本项目的目标是研究LTD在具有简单神经系统的动物的学习和记忆中的作用。 希望 通过在相对简单的生物体中研究LTD的细胞机制及其在学习中的作用所获得的见解将有助于我们理解LTD在更复杂的生物体（包括人类）大脑中的机制和与学习相关的作用。为此，PI将在无脊椎生物体中研究LTD，海洋蜗牛Aaprosia californica 这种动物拥有相对简单的神经系统，并表现出几种简单的学习形式。此外，大量 已经知道了阿鲁西亚行为的神经机制。 PI先前已经表明，在失智症的神经系统中感觉和运动神经元之间的突触可以表现出LTD。PI将分析失智症中感觉和运动神经元之间的突触LTD的细胞机制。PI还将确定LTD是否在被称为长期习惯化的记忆缺失症所表现出的简单学习形式中发挥作用。这个项目的结果应该提供关于LTD的细胞机制和LTD在学习中发挥的作用的重要的一般见解。 预计这些见解将推进有关神经系统如何介导学习和记忆的知识。

LAY ABSTRACT IBN-9808930 Changes in the strength of connections (synapses) between neurons in the brain are believed by most neuroscientists to underlie learning and memory. Synapses in the brain may increase in strength, or decrease in strength, as a consequence of learning by an animal. One prominent form of a change in synaptic strength that occurs in the mammalian brain is known as homosynaptic long-term depression or LTD. LTD is a decrease in the strength of a synapse, lasting 60 minutes to hours, produced by low-frequency stimulation of a presynaptic neural pathway. Many synapses in a part of the brain known as the hippocampus exhibit LTD. Because the hippocampus plays an important role in learning and memory in mammals, it is thought that LTD might represent a neural mechanism of memory. Despite a half-decade of work on LTD in the hippocampus, however, relatively little is understood about the cellular mechanisms that underlie LTD. Furthermore, even less is understood regarding what role LTD of hippocampal synapses might play in learning and memory. Part of the difficulty is that the hippocampus is a complex structure. Moreover, the types of learning that involve the hippocampus are difficult to understand on a neurobiological level. The goal of the present project is to study the role of LTD in learning and memory in an animal with a simple nervous system. The hope is that the insights gained by studying the cellular mechanisms of LTD, and its role in learning, in a relatively simple organism will help us to understand the mechanisms and learning- related role of LTD in the brains of more complex organisms, including man. Toward this end the PI will study LTD in an invertebrate organism, the marine snail Aplysia californica. This animal possesses a relatively simple nervous system and exhibits several simple forms of learning. Furthermore, a great deal is already known about the neural mechanisms of Aplysia's behavior. The PI has previously shown that synapses between sensory and motor neurons in the nervous system of Aplysia can exhibit LTD. The PI will analyze the cellular mechanisms of LTD of the synapses between sensory and motor neurons in Aplysia. The PI will also determine whether LTD plays a role in a simple form of learning exhibited by Aplysia known as long-term habituation. The results of this project should provide important general insights regarding the cellular mechanisms of LTD and the role that LTD plays in learning. It is expected that these insights will advance knowledge about how nervous systems mediate learning and memory.