HYPOTHALAMIC CARDIOVASCULAR AFFERENT INTEGRATION

描述：下丘脑室旁核的自主神经元 (PVN)被认为对心血管和身体有重大影响 流体调节功能，通过其密集的神经支配的吻 延髓腹外侧区（RVLM）、孤束核（NTS）和 中间外侧细胞柱（IML）。 特别是，PVN神经元介导 交感神经对等张容量扩张和中枢神经系统的反应 β受体激活。 音量和渗透性传入信号是如何 在单个PVN神经元的水平上整合还不清楚。 的 提出的实验将测试神经元投射到大脑皮层的假设。 IML是心血管和交感神经系统的主要PVN底物。 对体积膨胀和消耗的反应。 神经通路连接着 PVN到RVLM、NTS和IML被假设为各自在以下方面发挥独特的作用： 对中枢渗透压刺激的反应。 综合对策 同时激活渗透性和体积敏感性传入神经， 假设涉及血管紧张素能和GABA能之间的相互作用 输入。 结合逆行转运和Fos蛋白染色， 用于比较这3个PVN传出神经中的每一个的相对程度， 通路响应于容量消耗和中枢高渗。 失活研究将用于确定每种途径如何参与 出血和高渗引起的反应。 对音量的反应 扩张，出血和中枢渗透刺激将在 单个PVN神经元轴突投射至RVLM、NTS和IML。 拮抗剂的离子电渗应用将用于确定作用 GABA能和血管紧张素能神经传递在介导这些 单位的回应。 结果将提供新的见解的作用 PVN产生的各种自主神经通路在维持容量和 渗透平衡

DESCRIPTION: Autonomic neurons in the hypothalamic paraventricular nucleus (PVN) are considered to have a major influence on cardiovascular and body fluid regulatory functions through their dense innervation of the rostral ventrolateral medulla (RVLM), the nucleus tractus solitarius (NTS) and the intermediolateral cell column (IML). In particular, PVN neurons mediate sympathetic responses to both isotonic volume expansion and central osmoreceptor activation. How volume and osmotic afferent signal s are integrated at the level of single PVN neurons is not understood. The proposed experiments will test the hypothesis that neurons projecting to the IML are a primary PVN substrate for the cardiovascular and sympathetic responses to volume expansion and depletion. Neural pathways connecting the PVN to the RVLM, NTS and IML are hypothesized to each play a unique role in the response to central osmotic stimulation. Integrated responses to simultaneous activation of osmotic and volume-sensitive afferents is hypothesized to involve interactions among angiotensinergic and GABAergic inputs. Combining retrograde transport and Fos protein staining will be used to compare the relative degree to which each of these 3 PVN efferent pathways responds to volume depletion and central hyperosmolality. Inactivation studies will be used to determine how each pathway participates in hemorrhage- and hyperosmolality-induced responses. Responses to volume expansion, hemorrhage and central osmotic stimulation will be compared among individual PVN neurons with axonal projections to the RVLM, NTS and the IML. Iontophoretic application of antagonists will be used to determine the role of GABAergic and angiotensinergic neurotransmission in mediating these single unit responses. The results will provide new insight into the role of diverse autonomic pathways arising from the PVN in maintaining volume and osmotic homeostasis.