Homosynaptic Long-Term Depression: Mechanisms and Role in Learning

大脑中神经元之间连接(突触)强度的变化被大多数神经科学家认为是学习和记忆的基础。由于动物的学习，大脑中的突触可能会增加强度，也可能会减少强度。哺乳动物大脑中发生的突触强度变化的一种突出形式被称为同型突触长期抑郁或LTD。LTD是一种突触强度的下降，持续60分钟到几个小时，由低频刺激突触前神经路径产生。大脑中被称为海马体的部分有许多突触。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被认为可能代表了一种记忆的神经机制。然而，尽管在海马区对LTD进行了五年的研究，但对LTD背后的细胞机制了解相对较少。此外，关于海马区突触在学习和记忆中可能扮演的角色，人们更是知之甚少。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。本项目的目的是研究LTD在具有简单神经系统的动物学习和记忆中的作用。希望通过研究LTD在相对简单的生物体中的细胞机制及其在学习中的作用而获得的见解将有助于我们理解LTD在包括人类在内的更复杂生物体的大脑中的机制和与学习相关的角色。为此，PI将对一种无脊椎动物--海洋蜗牛--海螺进行研究。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，关于海兔行为的神经机制已经有了很大的了解。PI先前已经证明海兔神经系统中感觉神经元和运动神经元之间的突触可以表现为LTD。PI将分析海兔感觉神经元和运动神经元之间突触的LTD的细胞机制。PI还将决定LTD是否在海兔表现出的一种被称为长期习服的简单学习形式中发挥作用。这个项目的结果应该会对LTD的细胞机制和LTD在学习中所起的作用提供重要的一般性见解。预计这些见解将促进对神经系统如何调节学习和记忆的了解。

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.