NEUROMODULATOR INFLUENCES ON PREFRONTAL CORTICAL FUNCTION

神经调节剂对前额皮质功能的影响

• 批准号: 8584568
• 负责人: David T Blake
• 金额: $ 38.91万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8584568
• 关键词: Acetylcholine; Acetylcholinesterase Inhibitors; Age; Age-associated memory impairment; Alzheimer' s Disease; Animal Model; Antipsychotic Agents; Area; Attention; Basal Nucleus of Meynert; Behavior; Behavioral; Biological Models; Brain; Cerebral cortex; Cholinergic Agents; Cholinergic Agonists; Cholinesterase Inhibitors; Chronic; Clinical; Cognition; Cognitive; Corpus striatum structure; Decision Making; Deep Brain Stimulation; Dementia; Effectiveness; Effectiveness of Interventions; Electrodes; Enhancers; Evaluation; Impaired cognition; Implant; Injury; Intervention; Lateral; Memory; Mental disorders; Microelectrodes; Modeling; Monkeys; Muscarinic Acetylcholine Receptor; Muscarinic Antagonists; Nerve Degeneration; Neurobiology; Neuromodulator; Neurons; Neurotransmitters; Nicotine; Nicotinic Antagonists; Nicotinic Receptors; Parkinson Disease; Performance; Pharmaceutical Preparations; Pharmacology; Prefrontal Cortex; Primates; Process; Relative (related person); Research; Role; Schizophrenia; Scopolamine; Series; Short-Term Memory; Source; Stimulus; Symptoms; Synapses; System; Testing; Time; Traumatic Brain Injury; awake; basal forebrain; behavioral pharmacology; cholinergic; clinically relevant; cognitive function; cognitive rehabilitation; control trial; donepezil; executive function; flexibility; improved; neurophysiology; nonhuman primate; public health relevance; relating to nervous system; research study; response; successful intervention

DESCRIPTION (provided by applicant): A decline in cognitive functions such as attention, memory, and decision making is observed in a series of neurodegenerative conditions and mental illnesses. Cholinergic drugs (acetylcholine agonists and acetylcholinesterase inhibitors) can reverse these symptoms. Despite the known effectiveness of cholinergic drugs in improving cognitive function, the neuronal mechanisms of action in cortical areas involved in these processes, such as the prefrontal cortex are poorly understood. This project will investigate the effects of cholinergic drugs on prefrontal cortical activity during the execution of cognitive task and the effects of stimulation of the Nucleus Basalis, the main source of endogenous cortical acetylcholine. Neurophysiological recordings will be performed by a chronically implanted array of microelectrodes over the prefrontal cortex during the systemic administration of cholinergic agents and deep brain stimulation in a non- human primate model. The experiments will allow us to understand the effects of cholinergic agents in the prefrontal cortex associated with cognitive performance. They will also evaluate the relative effectiveness of drug administration compared to deep brain stimulation. Our research will also provide a primate model for the evaluation of new types of drugs that can potentially improve cognitive rehabilitation following injury or illness.

描述（由申请人提供）：在一系列神经退行性疾病和精神疾病中观察到认知功能（如注意力、记忆力和决策能力）下降。胆碱能药物（乙酰胆碱激动剂和乙酰胆碱酯酶抑制剂）可以逆转这些症状。尽管已知胆碱能药物在改善认知功能方面的有效性，但对参与这些过程的皮层区域（如前额叶皮层）的神经元作用机制知之甚少。本研究将探讨胆碱能药物对认知任务执行过程中前额叶皮层活动的影响，以及刺激基底核（皮层内源性乙酰胆碱的主要来源）的影响。在非人灵长类动物模型中，在全身给予胆碱能药物和脑深部刺激期间，将通过在前额皮质上长期植入微电极阵列进行神经生理学记录。这些实验将使我们能够了解前额叶皮层中胆碱能药物与认知表现相关的影响。他们还将评估与深部脑刺激相比，药物管理的相对有效性。我们的研究还将提供一个灵长类动物模型，用于评估新型药物，这些药物可能会改善受伤或疾病后的认知康复。