DOPAMINE INTERACTIONS WITH HIPPOCAMPAL MOSSY CELLS

项目描述。苔藓细胞是控制海马区信息流的关键细胞 它们是新生的成年颗粒神经元的第一个兴奋性输入。苔藓细胞 因此在调节海马区功能方面对神经精神健康和功能障碍有重要作用。 尽管多巴胺调节海马区的突触功能和可塑性，但特定的细胞靶点 多巴胺相互作用的性质尚不清楚。间接证据表明苔藓细胞 将多巴胺输入到海马体结构门区的特权接受者。这一证据驱使 我们的假设有待功能测试，即苔藓细胞是内源性多巴胺的唯一接受者。 在门区帮助解释苔藓细胞是特权受体的行为，我们假设多巴胺起作用 通过传统的突触接触而不是体积测量。我们将使用光遗传刺激 探查多巴胺和其他儿茶酚胺输入到苔藓细胞和门部其他细胞的技术 描述生理多巴胺反应的性质。在第二阶段的审讯中，我们将使用 在肺门细胞中表达的基于通道的生物传感器来测试多巴胺暴露于 苔藓细胞是通过传统的突触接触，而不是通过体积信号。我们的研究 通过假设DA在细胞中的细胞特异性作用来阐明令人费解的稀疏的DA神经支配 通过海马体控制信息流的类型。成功完成这些研究将提供 更广泛地研究DA对海马环路的影响及其作用的工具和初步数据 与神经精神健康和功能障碍相关的行为中的特定细胞相互作用。

Project Description. Mossy cells are pivotal cells governing information flow through the hippocampal formation, and they represent the first excitatory inputs to newly born granule neurons in the adult. Mossy cells therefore have an important role in governing hippocampal function in neuropsychiatric health and dysfunction. Although dopamine modulates synaptic function and plasticity in the hippocampus, the specific cellular targets and the nature of dopamine interactions are unclear. Circumstantial evidence suggests that mossy cells are privileged recipients of dopamine input to the hilus region of the hippocampal formation. This evidence drives our hypothesis, to be functionally tested, that mossy cells are the sole recipients of endogenous dopamine actions in the hilus To help explain mossy cells as privileged recipients, we hypothesize that dopamine acts through conventional synaptic contacts rather than volumetrically. We will use optogenetic stimulation techniques to probe dopamine and other catecholamine inputs to mossy cells and other cells of the hilus to characterize the nature of physiological dopamine responses. In a second level of interrogation, we will use channel-based biosensors expressed in cells of the hilus to test the hypothesis that dopamine exposure of mossy cells is through conventional synaptic contacts rather than through volumetric signaling. Our studies elucidate the puzzling sparse DA innervation of the hilus by hypothesizing cell-specific actions of DA at a cell type that gates information flow through the hippocampus. Successful completion of these studies will provide tools and preliminary data for a more expansive examination of DA effects on hippocampal circuitry and role of specific cellular interactions in behaviors relevant to neuropsychiatric health and dysfunction.