DOPAMINE ACTIONS ON HIPPOCAMPO-PREFRONTAL TRANSMISSION

多巴胺对海马前额传递的作用

• 批准号: 2519695
• 负责人: David B Carr
• 金额: $ 1.45万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2519695
• 关键词: afferent nerve; dopamine; dopamine antagonists; electrostimulus; frontal lobe /cortex; hippocampus; laboratory rat; neural transmission; neuropharmacology

The hippocampal formation and prefrontal cortex (PFC) have both been demonstrated to participate in working memory processes, and the hippocampo-prefrontal pathway has been suggested to play an important developmental role in the pathology of schizophrenia. Dopamine (DA) afferents from the ventral tegmental area (VTA) have also been implicated in the learning and memory functions of the hippocampus and the PFC, and dysfunction of ascending DA projections has been suggested to be involved in the neuropathology of schizophrenia. It is not known, however, whether DA afferents are able to modulate hippocampo-prefrontal transmission. The proposed research will utilize in vivo neurophysiological methods in rats to examine the ability of DA, applied locally or released by VTA stimulation. to act on this pathway both at the cell body level and in the terminal field. In Study 1, the actions of DA will be recorded on hippocampal neurons identified as projecting to the PFC. In Study 2, the ability of DA to modulate the response of PFC neurons to hippocampal stimulation will be examined. In Study 3, the ability of DA to act presynaptically on hippocampal terminals will be examined by recording the terminal excitability of hippocampal afferents to the PFC. The mechanisms of DA action that are identified in these studies will improve the understanding of its role in cognitive and affective functions, as well as its potential contribution to the pathophysiology and treatment of psychiatric and neurological disorders.

海马结构和前额皮质（PFC）均已被 被证明参与工作记忆过程，并且 海马-前额叶通路被认为发挥着重要作用 精神分裂症病理学中的发育作用。多巴胺 (DA) 来自腹侧被盖区（VTA）的传入神经也受到影响 海马体和前额叶皮层的学习和记忆功能，以及 DA 投射上升功能障碍被认为与此有关 在精神分裂症的神经病理学中。然而，尚不清楚是否 DA 传入神经能够调节海马-前额叶的传递。这 拟议的研究将利用大鼠体内神经生理学方法 检查本地应用或VTA发布的DA的能力 刺激。在细胞体水平和体内作用于该途径 终端字段。在研究 1 中，DA 的行为将被记录在 海马神经元被识别为投射到前额皮质。在研究 2 中， DA 调节 PFC 神经元对海马反应的能力 将检查刺激。在研究 3 中，DA 的行动能力 通过记录检查海马末端的突触前 海马传入前额皮质的终末兴奋性。这 这些研究中确定的 DA 作用机制将得到改善 了解其在认知和情感功能中的作用，例如 及其对病理生理学和治疗的潜在贡献 精神和神经系统疾病。