ROLE OF BASAL FOREBRAIN NEURONS IN SLEEP WAKE STATES

基底前脑神经元在睡眠觉醒状态中的作用

• 批准号: 6193769
• 负责人: BARBARA E JONES
• 金额: $ 15万
• 依托单位: MCGILL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-06 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6193769
• 关键词: REM sleep; acetylcholine; anesthesia; behavioral /social science research tag; electroencephalography; gamma aminobutyrate; glutamates; immunocytochemistry; laboratory rat; neural information processing; neurons; prosencephalon; sleep; urethan; wakefulness

The long-term goal of this research is to understand the nerual and chemical mechanisms that generate the different states of the brain and organism: waking (W), slow wave sleep (SWS) and paradoxical sleep (PS or rapid eye movement sleep, REM). During these states, the activity of the cerebral cortex undergoes fundamental changes, which are importantly determined by modulatory inputs from the basal forebrain. In human disease, lesions in this area can result in deficits in cortical activation and arousal, yet also in SWS. The aim of the proposed research is to identify by their anatomical features and neurotransmitters, including acetylcholine, GABA and glutamate, those basal forebrain neurons which are responsible for cortical activation that occurs during W and PS, and those which are reciprocally involved in cortical deactivation that occurs during SWS. Moreover, whether basal forebrain neurons, including cholinergic, GABAergic and possibly glutamatergic cells, modulate cortical activity in a rhythmic manner during cortical activation will be tested according to the thesis that such rhythmic modulation may provide a mechanism for integrated coherent activity across cortical regions. In a first series of experiments, neurons will be recorded by extracellular (or intracellular) technique in urethane-anesthetized rats to be characterized according to their discharge (or membrane) properties in relation to the cortical electroencephalogram (EEG) during undisturbed, irregular slow wave EEG and during stimulus- evoked, activated EEG. The electrophysiologically characterized neurons will be labelled with neurobiotin by juxtacellular (or intracellular) technique, revealed as cholinergic, GABAergic or possibly glutamatergic by dual fluorescent staining and delineated according to their somatodendritic morphology and axonal projections. In a subsequent experimental series, basal forebrain neurons will be recorded by extracellular technique in head-restrained animals to be characterized according to their discharge in relation to the EEG during natural states of W, SWS and PS. Again, they will be labelled by juxtacellular technique for subsequent identification as cholinergic, GABAergic or possibly glutamatergic and for delineation of their efferent projections. These studies will for the first time identify the specific neurons that are critically involved in state determination and reveal the discharge/membrane properties, chemical neurotransmitters and efferent projections by which they modulate cerebral activity across the sleep-wake cycle.

这项研究的长期目标是了解产生大脑和生物体不同状态的神经和化学机制：醒来（W），慢波睡眠（SWS）和矛盾的睡眠（PS或快速眼动运动睡眠，REM）。 在这些状态期间，大脑皮层的活性经历了基本变化，这些变化是由基础前脑的调节输入确定的。 在人类疾病中，该区域的病变可能导致皮质激活和唤醒的缺陷，但也会导致SWS。 拟议研究的目的是通过其解剖学特征和神经递质（包括乙酰胆碱，GABA和GABA和谷氨酸）来识别那些在W和PS期间导致皮质激活的基础前脑神经元，以及在SWS期间与皮质解脱相互涉及的皮质激活。 此外，是否在皮质激活期间以节奏方式调节皮质活性，包括胆碱能，GABA能和可能的基础前脑神经元，是否会根据这种节律调节可以为整个皮质区域的整合相干活性提供机制来测试皮质活性。 在第一系列的实验中，将通过尿双氨酸 - 动工大鼠的细胞外（或细胞内）技术记录神经元，以根据其排放（或膜）特性来表征与皮质电脑电图（EEG）相关的分泌物（或膜）特性。 电生理学特征的神经元将通过并置（或细胞内）技术标记为神经生物素，以双重荧光染色为胆碱能，GABA能或可能是谷氨酸剂，并根据其Somatendendritic形态和轴突构型通过双重荧光染色和谷氨酸剂。 在随后的实验系列中，基础前脑神经元将通过颅骨外的动物中的细胞外技术记录，以根据其在W，SWS和PS的自然状态期间根据EEG的排放来表征它们。 同样，它们将通过并列技术标记，以随后的鉴定为胆碱能，GABA能或可能是谷氨酸能的鉴定，并描述了其传递预测。 这些研究将首次确定与状态确定至关重要的特定神经元，并揭示出排放/膜特性，化学神经递质和传出投影，它们可以在整个睡眠效果周期调节大脑活性。