DA-GABA modulation of cortical ACh release

描述（由申请人提供）：丘脑核（NAC）是分布式神经系统中的关键区域，其整合了目标导向行为的基本信息。注意功能，包括对刺激的检测和选择，以及对所选刺激的适当处理，有助于目标导向行为。在这个更新的应用程序中，我们提出，动机和注意力的过程之间的整合是介导的相互作用，nasamatergic和多巴胺能输入NAC和随后的招聘NAC神经元合奏和他们的预测基底前脑皮质胆碱能系统（BFCS）。BFCS支配所有皮层区域，通常控制皮层信息处理。在行为上，BFCS已被证明介导注意功能的重要方面。拟议的研究将利用体内微透析、脑内注射和操作行为的组合来揭示同一动物的前额叶皮层（RFC）、NAC和基底前脑（BF）内的协调神经化学活性。我们将确定NAC中谷氨酸（Glu）和多巴胺（DA）之间的相互作用对RFC中乙酰胆碱（ACh）释放和注意力表现的功能后果。我们建议，注意力的表现，而不是当动物是在休息，特别是注意力的表现，触发的动机增强注意力的能力的挑战，将选择性地招募这个PFC-NAC-BF电路。最后，我们将确定这些功能之间的相互作用NAC谷氨酸和DA和皮质乙酰胆碱是如何改变的动物持续病变的腹侧海马作为新生儿或成人。腹侧海马在早期发展过程中的病变是一个广泛使用的精神分裂症的动物模型和文件的Glu/DA在NAC和ACh在RFC中的失调，以及注意力处理的障碍，将进一步验证这一重要的模型。总的来说，这些研究与重要的公共卫生问题有关。几种神经精神疾病被认为反映了这种分布式神经回路的失调，这些神经回路在注意力和相关执行功能的认知障碍中表现出来。这些疾病包括药物成瘾，ADHD和精神分裂症。拟议的研究应进一步发展和验证动物模型，形成这些健康相关领域转化研究的基础。

DESCRIPTION (provided by applicant): The nucleus accumbens (NAC) is a key region in a distributed neural system that integrates essential information underlying goal-directed behavior. Attentional functions, including the detection and selection of stimuli, and the appropriate processing of selected stimuli are instrumental for goal-directed behavior. In this renewal application, we propose that the integration between motivational and attentional processes is mediated by interactions between glutamatergic and dopaminergic inputs to NAC and the subsequent recruitment of NAC neuronal ensembles and their projections to the basal forebrain cortical cholinergic system (BFCS). The BFCS innervates all cortical areas and generally gates cortical information processing. Behaviorally, the BFCS has been demonstrated to mediate essential aspects of attentional functions. The proposed studies will utilize a combination of in vivo microdialysis, intracerebral injections, and operant behavior to reveal the coordinated neurochemical activity within the prefrontal cortex (RFC), NAC, and basal forebrain (BF) of the same animal. We will determine the functional consequences of interactions between glutamate (Glu) and dopamine (DA) in NAC for the release of acetylcholine (ACh) in RFC and attentional performance. We propose that attentional performance, as opposed to when the animal is at rest, specifically challenges on attentional performance which trigger the motivated enhancement of attentional capacities, will selectively recruit this PFC-NAC-BF circuit. Finally, we will determine how these functional interactions between NAC Glu and DA and cortical ACh are altered in animals sustaining lesions of the ventral hippocampus as neonates or as adults. Lesions of the ventral hippocampus during early development are a widely used animal model of schizophrenia and the documentation of dysregulations in Glu/DA in NAC and ACh in RFC, as well as impairments in attentional processing, will further validate this important model. Collectively, these studies have relevance to important public health implications. Several neuropsychiatric disorders are believed to reflect dysregulations in this distributed neural circuit that manifest themselves cognitively in impairments in attentional and related executive functions. These disorders include drug addiction, ADHD, and schizophrenia. The proposed research should further the development and validation of animal models that form the foundation of translational research in these health-related areas.