Department of Psychology, Rutgers University, Newark, USA.
Prog Neurobiol. 2011 Sep 15;95(1):1-13. doi: 10.1016/j.pneurobio.2011.05.007. Epub 2011 Jun 17.
The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction.
本次综述旨在描述纹状体中的分子机制，这些机制介导了工具性条件作用过程中的基于奖励的学习和行为控制。评估工具性条件作用的神经基础的实验揭示了纹状体中的功能回路，包括背侧和腹侧纹状体亚区，它们参与了动作-结果学习、刺激-反应学习以及由奖励相关线索对动作的动机控制。多巴胺（DA）和谷氨酸能神经传递在这些纹状体亚区中的整合被假设能够通过其在塑造突触可塑性和细胞兴奋性方面的作用来实现学习和行为控制。细胞外信号调节激酶（ERK）似乎对基于奖励的学习和行为控制特别重要，因为它对多巴胺和谷氨酸受体激活的敏感性及其在多种细胞功能中的参与。纹状体神经元中的 ERK 激活被提出在学习和表现因素中具有双重作用，这两个因素通过调节与可塑性相关的转录因子和调节细胞内在兴奋性来促进工具性条件作用。此外，滥用药物对 ERK 激活的干扰可能导致行为障碍，如成瘾。
