Van Acquoy Monique L, Nedelkoska Teodora, McMullan Simon, Burke Peter G R, Hildreth Cara M
Macquarie Medical School, Faculty of Medicine Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
Neuroscience Research Australia, Sydney, New South Wales, Australia.
Neuroendocrinology. 2025;115(6-7):564-575. doi: 10.1159/000545849. Epub 2025 Apr 14.
The subfornical organ (SFO) is a vital blood pressure-controlling region that elicits blood pressure changes likely via an excitatory (or glutamatergic) projection to the paraventricular nucleus of the hypothalamus (PVN). However, the role of this SFO-PVN pathway in blood pressure control has been poorly defined in the literature. As such, the present study aimed to examine the functional connectivity between the SFO neurons and the PVN and how they intersect to control blood pressure.
In Lewis rats (n = 10), glutamatergic SFO neurons (SFOglut) were transduced with channelrhodopsin via a CaMKIIa-promotor vector (pAAV9-CaMKIIa-hChR2(H134R)-EYFP). Under urethane anaesthesia, changes in blood pressure and renal and splanchnic nerve activities were recorded in response to photostimulation of SFOglut neurons before and after administration of an intravenous ganglionic blocker and V1a receptor antagonism and inhibition of the PVN via muscimol microinjection. Immunohistochemistry was used to examine the projections between the SFO and PVN.
Photostimulation of SFOglut neurons produced a frequency-dependent pressor response that was abolished by sympathetic ganglionic blockade but not by inhibiting the vasoactive hormone vasopressin. This pressor response depends on ongoing neuronal transmission within the PVN as it is abolished by bilateral PVN inhibition. Confirming this, we found dense projections from SFOglut neurons to magnocellular and parvocellular PVN neurons. Finally, photostimulation of SFOglut neurons elicited a peak increase in sympathetic nerve activity that was reversibly abolished by phenylephrine administration and abolished by inhibition of the PVN, suggesting that the neuronal circuitry underpinning this response is barosensitive.
The pressor response elicited by SFOglut neurons is largely mediated by barosensitive sympathetic nerve activity and dependent on the PVN.
穹窿下器（SFO）是一个重要的血压控制区域，可能通过对下丘脑室旁核（PVN）的兴奋性（或谷氨酸能）投射引起血压变化。然而，这条SFO - PVN通路在血压控制中的作用在文献中尚未明确界定。因此，本研究旨在探讨SFO神经元与PVN之间的功能连接以及它们如何相互作用以控制血压。
在10只Lewis大鼠中，通过CaMKIIa启动子载体（pAAV9 - CaMKIIa - hChR2(H134R) - EYFP）将通道视紫红质转导至谷氨酸能SFO神经元（SFOglut）。在乌拉坦麻醉下，在静脉注射神经节阻滞剂、V1a受体拮抗剂以及通过微量注射蝇蕈醇抑制PVN之前和之后，记录对SFOglut神经元进行光刺激时血压、肾神经和内脏神经活动的变化。采用免疫组织化学方法检测SFO与PVN之间的投射。
对SFOglut神经元进行光刺激产生频率依赖性升压反应，该反应可被交感神经节阻滞消除，但不能通过抑制血管活性激素血管加压素消除。这种升压反应依赖于PVN内持续的神经元传递，因为双侧PVN抑制可将其消除。证实这一点的是，我们发现从SFOglut神经元到PVN大细胞和小细胞神经元有密集投射。最后，对SFOglut神经元进行光刺激引起交感神经活动峰值增加，该增加可被去氧肾上腺素给药可逆性消除，并被PVN抑制消除，这表明支持该反应的神经回路对压力敏感。
SFOglut神经元引发的升压反应主要由对压力敏感的交感神经活动介导，并依赖于PVN。
