SYNAPTIC ORGANIZATION OF BASAL FOREBRAIN PROJECTIONS

这项研究的目标是提供生理学和 神经通路突触组织的药理学分析 从大鼠的基底前脑到边缘系统和丘脑，以及 从边缘系统到基底的相互投射 前脑。第一，传出投射的生理学研究 取自大鼠的基底前脑将继续。工作将会 专注于斜角带核的投射 Broca、无名质和毗邻基底前脑至 丘脑内侧背核和网状核。为了实现 这个目标，会刺激基底前脑 电和突触电位对此作出反应 刺激将被记录在丘脑的细胞内。 靶细胞将通过细胞内注射HRP进行鉴定。 第二，将进行药理分析，研究 推测从基底前脑到边缘的胆碱能投射 皮质(具体地说是内嗅皮层、下复合体和 扣带回皮质)；丘脑(特别是内嗅皮层， 丘脑)； (特别是背内侧核和网状核)。它是 假设靶主细胞通过慢速刺激而兴奋 代理M_1受体。胆碱能激动剂和 拮抗剂将在电击期间应用于离子电泳法 刺激基底前脑。刺激的效果将 与胆碱能激动剂的作用相比较， 胆碱能拮抗剂对诱发电位的阻断作用 突触将被确定。 第三，投射到丘脑核团的生理作用 亚束复合体的斜带将被确定。 由于这种突起的生理作用尚不清楚，因此在 活体细胞内记录实验将在 建立边缘皮质在斜角线上的突触作用 条带神经元。 这些细胞内和药理学研究解决了问题 最好在系统层面上完整地研究，在 活体准备。基底前脑的胆碱能细胞，以及 他们的边缘目标在阿尔茨海默氏症中似乎经历了退化 疾病。因此，对这个神经系统的了解可以 提供与此相关的心理病理学的洞察力 疾病。

The objectives of this research are to provide physiological and pharmacological analyses of the synaptic organization of pathways from the rat basal forebrain to the limbic system and thalamus, and reciprocal projections from the limbic system to the basal forebrain. First, physiological studies of efferent projections from the rat basal forebrain will be continued. Work will concentrate on projections from the nucleus of the diagonal band of Broca, substantia innominata, and adjacent basal forebrain to the thalamic mediodorsal and reticular nuclei. In order to achieve this objective, the basal forebrain will be stimulated electrically, and synaptic potentials in response to this stimulation will be recorded intracellularly in the thalamus. Target cells will be identified by intracellular HRP injection. Second, a pharmacological analysis will be performed, studying putative cholinergic projections from the basal forebrain to limbic cortex (specifically entorhinal cortex, subicular complex, and cingulate cortex); and thalamus (specifically entorhinal cortex, subicular complex, and cingulate cortex); and thalamus (specifically the mediodorsal and reticular nuclei). It is hypothesized that target principal cells are excited via slow- acting M1 muscarinic receptors. Cholinergic agonists and antagonists will be iontophoretically applied during electrical stimulation of the basal forebrain. The effect of stimulation will be compared to the action of the cholinergic agonists, and the efficacy of the cholinergic antagonists in blocking the evoked synaptic will be determined. Third, the physiological action of projections to the nucleus of the diagonal band from the subicular complex will be determined. Since the physiological action of this projection is unknown, in vivo intracellular recording experiments will be valuable in establishing the synaptic action of the limbic cortex on diagonal band neurons. These intracellular and pharmacological studies attack problems that can best be studied at the systems level in the intact, in vivo preparation. The cholinergic cell of the basal forebrain, and their limbic targets appear to undergo degeneration in Alzheimer's disease. An understanding of this neuronal system can therefore provide insight into the psychopathology associated with this disease.