NEUROMODULATOR INFLUENCES ON PREFRONTAL CORTICAL FUNCTION

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的下降，如注意力，记忆力和决策能力。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，但参与这些过程的皮层区域（如前额皮质）的神经元作用机制尚不清楚。本项目将研究胆碱能药物在认知任务执行过程中对前额叶皮层活动的影响，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，神经生理学记录将通过在前额叶皮层长期植入微电极阵列，在系统给予胆碱能药物和深部脑刺激时进行。这些实验将使我们了解胆碱能药物在前额皮质中与认知表现相关的作用。他们还将评估药物管理与深部脑刺激的相对有效性。我们的研究也将为评估可能改善受伤或疾病后认知康复的新型药物提供灵长类动物模型。

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.