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：
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
项目类别：
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&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 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

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，记忆和决策）的认知功能下降。胆碱能药物（乙酰胆碱激动剂和乙酰胆碱酯酶抑制剂）可以扭转这些症状。尽管胆碱能药物在改善认知功能方面具有已知的有效性，但在这些过程中涉及的皮质区域的作用机制，例如前额叶皮层，却鲜为人知。该项目将研究胆碱能药物在执行认知任务期间对前额叶皮质活性的影响，以及刺激基底核的刺激的影响，核基底是内源性皮质乙酰胆碱的主要来源。神经生理记录将在胆碱能剂的系统给药期间由长期植入的微电极在前额叶皮层上进行，并在非人类灵长类动物模型中进行深脑刺激。这些实验将使我们能够了解胆碱能剂在与认知性能相关的前额叶皮层中的影响。与深脑刺激相比，他们还将评估药物给药的相对有效性。我们的研究还将为评估新类型的药物提供灵长类动物模型，这些药物有可能改善受伤或疾病后的认知康复。