SYNAPTIC ORGANIZATION OF RETROHIPPOCAMPAL PATHWAYS

该项目的广泛、长期目标是提供 大脑皮层突触组织的生理学和药理学分析 大鼠丘下复合体的传出、传入和内在联系 和内嗅皮层。第一，传出投射的生理学研究 从这些结构将继续。工作将集中在 下丘脑束下复合体和内嗅叶皮质向 前额叶皮质。为了实现这一目标，分会 复合体和内嗅皮层会受到电刺激，并突触 对这种刺激作出反应的电位将被记录在细胞内 在前额叶皮质。前额叶皮质的靶神经元将是 细胞内注射辣根过氧化物酶(HRP)以 建立其树突和轴突的形态。 第二，膝下投射的药理学分析 将复合体传导到内嗅皮层，使用多管 离子导入技术。药理学研究将被设计为 检验内嗅主兴奋性反应的假设 抑制细胞是由谷氨酸能传递介导的； 抑制反应由GABA能传递介导，继而 局部抑制性神经元的谷氨酸能兴奋(前馈 抑制)。GABA A和GABA B受体的特定拮抗剂将是 用于确定负责的受体亚型(S) 抑制反应。 第三，膝下投射的药理学分析 复合体和内嗅觉皮质至杏仁核和前额叶皮质 将会进行。推测谷氨酸能和GABA能 受体在这些靶点内介导前馈抑制，并努力 将集中于确定受体亚型的作用。 第四，投射对膝下复合体的生理作用 以及来自前额叶皮质的内嗅皮层将被确定。在……里面 具体地说，建议1)确定抑制反应是否 前额叶刺激由位于脑内的抑制性神经元介导 下复合体和内嗅皮层；2)建立 反应性靶点的树突形态和轴突投射模式 通过细胞内注射HRP对神经元进行诱导。 拟议的细胞内和药理学研究针对的问题是 最好的研究是在完整的、活体的系统水平上 准备工作。下丘脑复合体和内嗅皮层参与 医学难治性颞叶癫痫，似乎是早期目标 阿尔茨海默病的细胞死亡。因此，更好地理解 这些神经系统可以提供对病理生理学的洞察 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.