Plasticity and learning in a corticostriatal network

描述（由申请人提供）：近年来，大量的兴趣集中在多巴胺-谷氨酸相互作用在神经可塑性、学习和记忆以及成瘾控制中的作用。这两种神经递质系统广泛分布于大脑皮层、边缘系统和基底神经节的许多区域，在这些区域中它们似乎在动机和联想信息处理中起着整合作用。目前认为，这些系统的协调神经信号传导，特别是通过多巴胺D1和谷氨酸N-甲基-D-天冬氨酸（NMDA）受体，是触发细胞内转导和转录级联的关键事件，导致基因表达，突触可塑性和最终行为的长期变化。成瘾性药物还在结构、细胞、分子和基因组水平上诱导长期神经适应，主要是通过它们对多巴胺能和多巴胺能回路的影响。这种药物诱导的神经适应可能导致异常的信息处理和行为，导致决策能力差，失去控制，以及成瘾的强迫性。因此，关于多巴胺和谷氨酸介导的神经网络的正常行为作用的进一步信息可能有助于阐明成瘾的本质及其治疗。本研究将探讨谷氨酸和多巴胺编码的神经回路在控制食欲工具学习中的作用。使用解剖，分子和行为的方法，我们将测试的假设，NMDA和DI受体介导的可塑性在多个节点的神经网络控制新的适应性运动学习。

DESCRIPTION (provided by applicant): In recent years a great amount of interest has focused on the role of dopamine-glutamate interactions in the control of neural plasticity, learning and memory, and addiction. These two neurotransmitter systems are found widely distributed in many regions of cortex, limbic system, and basal ganglia, where they appear to play an integrative role in motivational and associative information processing. It is currently believed that coordinated neural signaling of these systems, particularly through the dopamine D1 and glutamate N-methyI-D-aspartate (NMDA) receptors, is a critical event in triggering intracellular transductional and transcriptional cascades that lead to long-term changes in gene expression, synaptic plasticity, and ultimately behavior. Addictive drugs also induce long-term neuroadaptations at the structural, cellular, molecular, and genomic levels, primarily through their impact on dopaminergic and glutamatergic circuits. Such drug-induced neuroadaptations may contribute to abnormal information processing and behavior, resulting in poor decision-making, loss of control, and compulsivity that characterized addiction. Thus, further information regarding the normal behavioral role of dopamine- and glutamate-mediate neural networks may help to shed light on the nature of addiction and its treatment. In this research project, the role of glutamate- and dopamine-coded neural circuitry in the control of appetitive instrumental learning will be explored. Using anatomical, molecular, and behavioral approaches, we will test the hypothesis that NMDA- and Dl-receptor mediated plasticity within multiple nodes of a neural network controls new adaptive motor learning.