ELECTROPHYSIOLOGY OF THE PREFRONTAL CORTEX

前额皮质的电生理学

• 批准号: 2891029
• 负责人: PATRICIO O'DONNELL
• 金额: $ 18.53万
• 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/2891029
• 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。