INFORMATION PROCESSING IN THE NUCLEUS ACCUMBENS

描述(改编自申请人的摘要)：多巴胺能投射到 伏隔核是临床有效抗精神病药物的靶点， 它被认为与精神分裂症的病理生理学有关。此外, 几项成像研究表明，许多皮质区域也 受累于这种疾病，包括前额叶皮质和海马体 队形。确定这些系统如何相互作用将提供 我们对这一现象的神经基础的理解取得了重大进展 毁灭性的混乱。伏隔核是大脑的一个区域，它可以 将这些看似无关的神经系统集成到一个概念中 框架。事实上，这个大脑区域几乎与每一个区域都有联系 与这种疾病有牵连。揭示信息整合的机制 伏隔核是我们研究工作的一个主要目标。在这 建议，我们计划评估多巴胺、海马区和其他边缘区域的作用 控制伏隔核细胞活动的输入。我们会研究 这些输入对活动状态和静默状态之间的转换的影响 伏隔核神经元表现出。大鼠大脑皮质吞吐能力的海马区门控 我们先前提出的伏隔核，以及参与 控制前额-伏隔反应的其他边缘输入将是 用海马区电活动的同步记录进行评估 还有伏隔核。单胺的作用(也牵涉到 精神分裂症)对伏隔核细胞兴奋性和活动状态的影响 使用体内和体外细胞内记录进行研究。最后， 依赖缝隙连接的信息传递的潜在作用 伏隔神经元对活动状态的同步性将被评估 从成对的对进行体外双全细胞钳制记录 细胞。

DESCRIPTION (Adapted from Applicant's abstract): The dopaminergic projection to the nucleus accumbens is the target of clinically effective antipsychotics and it has been implicated in the pathophysiology of schizophrenia. In addition, several imaging studies have shown a number of cortical regions to be also affected in this disorder, including the prefrontal cortex and hippocampal formation. Establishing how these systems interact with each other will provide a significant advance in our understanding of the neural basis of this devastating disorder. The nucleus accumbens is a brain region that could integrate these seemingly unrelated neural systems within a single conceptual framework. Indeed, this brain region has connections with virtually every area implicated in this disease. Unveiling the mechanisms of information integration in the nucleus accumbens is a major goal in our research efforts. In this proposal, we plan to assess the role of dopamine, hippocampal and other limbic inputs in the control of nucleus accumbens cell activity. We will study the impact of these inputs on the transitions between the active and silent states accumbens neurons exhibit. The hippocampal gating of cortical throughput in the nucleus accumbens previously proposed by us, as well as the involvement of other limbic inputs in the control of prefrontal-accumbens responses will be assessed with simultaneous recordings of electrical activity in the hippocampus and the nucleus accumbens. The actions of monoamines (also implicated in schizophrenia) on nucleus accumbens cell excitability and activity states will be studied using both in vivo and in vitro intracellular recordings. Finally, the potential role of gap junction-dependent transfer of information between accumbens neurons on the synchronization of active states will be assessed by performing dual whole-cell clamp recordings in vitro from pairs of coupled cells.