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NEUROMODULATOR INFLUENCES ON PREFRONTAL CORTICAL FUNCTION

神经调节剂对前额皮质功能的影响

基本信息

批准号：
9269276
负责人：
David T Blake
金额：
$ 38.41万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9269276
关键词：
Acetylcholine Acetylcholinesterase Inhibitors Age-associated memory impairment Aging Alzheimer&apos 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 Research Role Schizophrenia Scopolamine Series Short-Term Memory Source Stimulus Symptoms Synapses System Testing Time Traumatic Brain Injury awake basal forebrain behavioral pharmacology cholinergic clinical effect clinically relevant cognitive function cognitive performance cognitive process cognitive rehabilitation cognitive task control trial donepezil executive function experimental study flexibility improved neurophysiology nonhuman primate public health relevance relating to nervous system relative effectiveness response successful intervention

项目摘要

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（例如注意力、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有效，但参与这些过程的皮质区域（例如前额皮质）的神经元作用机制却知之甚少。该项目将研究胆碱能药物在执行认知任务期间对前额皮质活动的影响以及刺激基底核（内源性皮质乙酰胆碱的主要来源）的影响。在非人类灵长类动物模型中全身施用胆碱能药物和进行深部脑刺激期间，将通过在前额皮质上长期植入的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胆碱能药物对前额叶皮层与认知表现相关的影响。他们还将评估药物施用与深部脑刺激相比的相对有效性。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，这些药物有可能改善受伤或疾病后的认知康复。