ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEX

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。

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.