HYPOTHALAMIC CARDIOVASCULAR AFFERENT INTEGRATION

描述：下丘脑室旁核内的自主神经元 (PVN)被认为对心血管和身体有重大影响 通过其对吻部的密集神经支配发挥体液调节功能 延髓腹外侧核(RVLM)、孤束核(NTS) 中间外侧细胞柱(IML)。特别是，下丘脑室旁核神经元在 对等渗性体积膨胀和中枢的交感反应 渗透受体激活。S的音量和渗透传入信号 在单个下丘脑室旁核神经元水平上的整合尚不清楚。这个 拟议的实验将检验这样一种假设，即投射到 IML是心血管和交感神经的主要PVN底物 对成交量扩张和耗尽的反应。连接神经的神经通路 假设PVN到RVLM、NTS和IML各自在RVLM、NTS和IML中扮演独特的角色 对中枢渗透刺激的反应。对以下问题的综合回应 渗透和容量敏感传入的同时激活是 假设涉及血管紧张素能和GABA能之间的相互作用 投入。结合逆行转运和Fos蛋白染色将 用来比较这3种PVN传出的相对程度 通路对容量耗竭和中枢性高渗透压有反应。 失活研究将被用来确定每个途径是如何参与的 在出血和高渗透压诱导的反应中。对音量的反应 扩张、出血和中枢渗透刺激将在 有轴突投射至RVLM、NTS和IML的单个PVN神经元。 离子导入应用拮抗剂将确定其作用 GABA能和血管紧张素能神经递质在介导这些过程中的作用 单个单位的响应。这一结果将为我们提供对这一角色的新见解 PVN产生的多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.