Postactivation potentiation models of memory

大多数神经科学家现在认为，信息是通过改变脑细胞（神经元）之间的连接（突触）储存在大脑中的。 这允许对最终编码存储器的电路进行重构。 然而，这些改变的连接是高度分布的，它们嵌入在数百万个保持不变的连接的矩阵中。 不仅很难确定哪些连接受到影响，而且我们通常无法确定哪些神经元，甚至哪些神经元组参与了存储过程。 因此，要研究真实的记忆的生理机制是非常困难的。 另一种方法是研究可能利用相同或相似机制的其他现象的机制，特别是那些产生突触连接的受控改变的现象。 其中一种现象是长时程增强（LTP）。 如果将某些模式的电刺激直接应用于特定的神经通路，则该通路与其神经元靶点之间的连接强度可以在很长一段时间内增加。 这种现象可以通过实验分析来验证，在过去的三十年里，它在神经科学界受到了极大的关注。 我实验室的大部分工作都是针对这种可塑性在大脑皮层和皮层下区域的表达所适用的规则进行研究。 下一个资助学期的工作重点是两个系统中的LTP，一个涉及运动控制和运动学习，另一个涉及情绪控制和动机。 这一研究将进一步加深我们对突触可塑性和记忆机制的认识。 此外，它还应提供有助于开发记忆障碍和药物滥用治疗方法的信息。

Most neuroscientists now believe that information is stored in the brain as an alteration in the connections (synapses) between brain cells (neurons).  This allows the restructuring of the circuitry that ultimately codes the memory.  These altered connections, however, are highly distributed, and they are embedded in a matrix of millions of connections that remain unaltered.  It is not only difficult to determine which connections are affected, we often cannot be certain which neurons, or even which groups of neurons, are participating in the storage process.  As a result, it is extraordinarily difficult to study the physiological mechanisms of real memory.  An alternative approach is to study the mechanisms of other phenomena that may utilize the same or similar mechanisms, particularly those that yield a controlled alteration of synaptic connectivity.  One such phenomenon is long-term potentiation (LTP).  If certain patterns of electrical stimulation are applied directly to specific neural pathways, the strength of the connections between that pathway and its neuronal target can be increased for long periods of time.  This phenomenon is amenable to experimental analysis, and it has received an enormous amount of attention in the neuroscience community over the last three decades.  Much of the work in my laboratory has been directed to the study of the rules that apply to this form of plasticity as it is expressed in cortical and subcortical brain regions.  The work that is proposed for the next grant term focuses on LTP in two systems, one involved in motor control and motor learning and the other in mood control and motivation.  This research will further our understanding of the mechanisms of synaptic plasticity and memory.  In addition, it should provide information that will facilitate the development of treatments for memory disorders and drug abuse.