Plasticity and learning in a corticostriatal network

描述(申请人提供)：近年来，人们对多巴胺-谷氨酸相互作用在神经可塑性、学习记忆和成瘾控制中的作用产生了极大的兴趣。这两种神经递质系统广泛分布于大脑皮层、边缘系统和基底节的许多区域，在动机和联想信息加工中起着整合作用。目前认为，这些系统的协调神经信号，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反应的关键事件，导致基因表达、突触可塑性和最终行为的长期变化。成瘾药物还可以在结构、细胞、分子和基因组水平上诱导长期的神经适应，主要是通过影响多巴胺和谷氨酸能回路。这种药物诱导的神经适应可能会导致异常的信息处理和行为，导致糟糕的决策，失去控制，以及以成瘾为特征的强迫症。因此，关于多巴胺和谷氨酸介导的神经网络正常行为作用的进一步信息可能有助于阐明成瘾的性质及其治疗。在这项研究项目中，谷氨酸和多巴胺编码的神经回路在控制食欲工具性学习中的作用将被探索。利用解剖学、分子和行为学的方法，我们将检验这一假设，即神经网络的多个节点内的NMDA和DL受体介导的可塑性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.