SYNAPTIC ORGANIZATION OF RETROHIPPOCAMPAL PATHWAYS

该项目的广泛和长期目标是提供 突触组织的生理学和药理学分析 大鼠下托复合体的传出、传入和内在联系 和内嗅皮层。首先，传出投射的生理学研究 这些结构将继续。工作将集中在 下托复合体和内嗅皮质向下丘脑的投射 前额皮质为了达到这个目的， 复合体和内嗅皮层将受到电刺激， 将在细胞内记录响应于该刺激的电位 大脑前额叶皮层前额叶皮层的目标神经元 细胞内注射辣根过氧化物酶（HRP）， 建立其树突和轴突形态。 第二，下托投射的药理学分析 复杂的内嗅皮层将进行，使用多管 离子电渗技术。药理学研究将设计为 检验内嗅原则中的兴奋性反应 和抑制性细胞是由谷氨酸能传递介导的;并且 抑制反应由GABA能传递介导，继发于 局部抑制性神经元的神经兴奋（前馈 抑制）。GABA A和GABA B受体的特异性拮抗剂将是 用于确定负责免疫应答的受体亚型。 抑制反应 第三，对海马下托投射的药理学分析 杏仁核和前额叶皮层的复合体和内嗅皮层 将进行。假设谷氨酸能和GABA能 受体介导这些靶点内的前馈抑制， 将集中精力确定受体亚型的作用。 第四，下托复合体投射的生理作用 和前额叶皮层的内嗅皮层。在 特别是，建议1）确定是否抑制反应， 前额叶刺激是由位于脑内的抑制性神经元介导的。 大脑下托复合体和内嗅皮层; 2）建立 树突形态和反应靶轴突投射的模式 神经元通过注射他们与HRP细胞内。 拟议的细胞内和药理学研究解决了以下问题， 最好在完整的体内系统水平上进行研究 准备.下托复合体和内嗅皮层参与了 药物难治性颞叶癫痫，似乎是早期目标 阿尔茨海默病中的细胞死亡。因此，更好地理解 这些神经元系统的研究可以提供对病理生理学的深入了解， 与这些疾病有关。

The broad, long-term objectives of this project are to provide physiological and pharmacological analyses of the synaptic organization of efferent, afferent, and intrinsic connections of the rat subicular complex and entorhinal cortex. First, physiological studies of efferent projections from these structures will be continued. Work will concentrate on projections from the subicular complex and entorhinal cortex to the prefrontal cortex. In order to achieve this objective, the subicular complex and entorhinal cortex will be stimulated electrically, and synaptic potentials in response to this stimulation will be recorded intracellularly in the prefrontal cortex. Target neurons in the prefrontal cortex will be injected intracellularly with horseradish peroxidase (HRP) in order to establish their dendritic and axonal morphology. Second, a pharmacological analysis of projections from the subicular complex to the entorhinal cortex will be conducted, using multibarrel iontophoretic techniques. The pharmacological studies will be designed to test the hypothesis that the excitatory responses in entorhinal principal and inhibitory cells are mediated by glutamatergic transmission; and that inhibitory responses are mediated by GABAergic transmission, secondary to glutamatergic excitation of local inhibitory neurons (feedforward inhibition). Specific antagonists of GABA A and GABA B receptors will be used in order to determine the receptor subtype(s) responsible for the inhibitory responses. Third, a pharmacological analysis of the projections from the subicular complex and entorhinal cortex to the amygdala and to the prefrontal cortex will be conducted. It is hypothesized that glutamatergic and GABAergic receptors mediate feedforward inhibition within these targets, and effort will be concentrated on establishing the roles of receptor subtypes. Fourth, the physiological action of projections to the subicular complex and entorhinal cortex from the prefrontal cortex will be determined. In particular, it is proposed 1) to establish whether inhibitory responses to prefrontal stimulation are mediated by inhibitory neurons located within the subicular complex and entorhinal cortex and 2) to establish the dendritic morphology and pattern of axonal projections of responsive target neurons by injecting them intracellularly with HRP. The proposed intracellular and pharmacological studies attack problems that can best be studied at the systems level in the intact, in vivo preparation. The subicular complex and entorhinal cortex participate in medically-refractory temporal lobe seizures, and appear to be early targets of cell death in Alzheimer's disease. Accordingly, a better understanding of these neuronal systems can provide insight into the pathophysiology associated with these diseases.