ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEX

前额皮质的电生理学

• 批准号: 6185815
• 负责人: PATRICIO O'DONNELL
• 金额: $ 19.15万
• 依托单位: ALBANY MEDICAL COLLEGE
• 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 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185815
• 关键词: electrophysiology; experimental brain lesion; frontal lobe /cortex; glutamate receptor; hippocampus; isolation /deprivation; laboratory rat; neural transmission; neurotransmitter agonist; neurotransmitter antagonist; schizophrenia

DESCRIPTION (Adapted from applicant's abstract): The interactions among the prefrontal cortex, hippocampus and dopaminergic systems are thought to play a role in schizophrenia. However, the nature of such interactions from a physiological perspective are not yet fully understood. Establishing how a hippocampal deficit impacts on physiological measures of prefrontal neuron activity and how dopamine modulates these interactions may provide a significant contribution towards establishing a comprehensive animal model of this devastating disorder. In this proposal, plans are presented to assess the impact of a number of manipulations in the hippocampal afferents to prefrontal cortical neurons intracellularly recorded in vivo: 1) determining the input responsible for the transitions to the active periods in prefrontal cortical neurons exhibiting a slow oscillation in their membrane potential and cell firing; 2) establishing the role of hippocampal afferents on such oscillations and their source input by assessing the effects of hippocampal stimulation and by performing similar experiments in animals with a hippocampal lesion; 3) assessing the effects of a neonatal hippocampal lesion on these interactions in adult animals as an initial attempt of testing the hypothesis of a developmental hippocampal disturbance resulting in hypofrontality; 4) testing the effects of rearing animals in social isolation on these interactions, with the aim to determine the actions of an environmentally-induced brain deficit that in many respects exhibits alterations resembling schizophrenia; and, 5) determining the glutamate receptor subtype involved in hippocampal-prefrontal interactions by studying the actions of glutamate receptor agonists and antagonists on synaptic responses in prefrontal cortical cells recorded in vivo.

描述(改编自申请者摘要)： 前额叶皮质、海马体和多巴胺能系统被认为在 在精神分裂症中扮演的角色。然而，这种交互的性质来自于 生理学角度还没有完全被理解。确定如何 海马区缺失对前额神经元生理指标的影响 活性以及多巴胺如何调节这些相互作用可能提供 对建立全面的动物模型做出了重大贡献 这场毁灭性的混乱。在这份提案中，计划被提交给 评估多种手法对海马区传入的影响 活体细胞内记录的前额叶皮质神经元：1) 确定负责过渡到活动期的输入 在前额叶皮质神经元中表现出缓慢的振荡 膜电位与细胞放电；2)确定海马区的作用 关于这种振荡的传入及其源输入通过评估 刺激海马区的效果，并通过在 有海马区损伤的动物；3)评估新生儿的影响 成年动物海马区损伤对这些相互作用的影响 海马区发育性障碍假说的验证尝试 导致额叶下垂；4)测试饲养动物在 在这些互动上的社会隔离，目的是确定 环境引起的大脑缺陷在许多方面的行为 表现出类似精神分裂症的改变；以及，5)确定 谷氨酸受体亚型参与海马-前额叶相互作用 通过研究谷氨酸受体激动剂和拮抗剂在血管内皮细胞中的作用 活体记录的前额叶皮质细胞的突触反应。