ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEX

描述（改编自申请人摘要）： 前额叶皮层、海马体和多巴胺能系统被认为是 在精神分裂症中的作用 然而，这种相互作用的性质， 生理角度尚未完全理解。 确定A 海马损伤对前额叶神经元生理指标的影响 活动和多巴胺如何调节这些相互作用可能提供了一个 为建立全面的动物模型做出了重大贡献 这种毁灭性的疾病。 在这份提案中，计划提出， 评估海马传入神经的一些操作的影响 前额叶皮层神经元细胞内记录在体内：1） 确定负责到活动时段的转换的输入 在前额皮质神经元中， 膜电位和细胞放电; 2）建立海马的作用 通过评估这种振荡的传入和它们的源输入， 海马刺激的影响，并进行类似的实验， 海马损伤的动物; 3）评估新生儿 海马损伤对成年动物这些相互作用的影响， 海马发育障碍假说的验证 导致额叶功能减退; 4）测试饲养动物的效果， 社会隔离对这些互动，目的是确定 环境引起的大脑缺陷在许多方面 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对 在体内记录的前额叶皮层细胞的突触反应。

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.