What the hippocampus tells the HPA axis: Hippocampal output attenuates acute stress responses via disynaptic inhibition of CRF+ PVN neurons.
What the hippocampus tells the HPA axis: Hippocampal output attenuates acute stress responses via disynaptic inhibition of CRF+ PVN neurons.
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DOI：
10.1016/j.ynstr.2022.100473
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发表时间：
2022-09
影响因子：
5
通讯作者：
Thompson, Scott M.
中科院分区：
文献类型：
--
作者：
Cole, Anthony B.;Montgomery, Kristen;Bale, Tracy L.;Thompson, Scott M.
关键词：
海马对糖皮质激素的释放施加抑制反馈。由于主要的海马传出投射是兴奋性的，因此假设这种抑制是由下丘脑或其他地方的抑制性神经元群介导的。这些区域可被海马传出神经兴奋并投射到下丘脑室旁核（PVN）的促肾上腺皮质激素释放因子（CRF）细胞。在PVN细胞或上游GABA能中间神经元中由海马输出引起的突触反应的直接证明先前尚未提供。在这里，我们使用病毒载体表达通道视紫红质（ChR）和增强型黄色荧光蛋白（EYFP）的锥体细胞在腹侧海马（vHip）的小鼠表达tdTomato在GABA或CRF表达神经元。我们观察到密集的神经支配的床核的终纹（BNST）标记的vHip轴突和稀疏标记的PVN内。在含有BNST和PVN的旁脑切片中使用全细胞电压钳记录，光刺激vHip末端在CRF+和GAD +细胞中引起快速兴奋性突触后电流（EPSC）和较长潜伏期的抑制性突触后电流（IPSC）。在20 Hz刺激序列中，CRF +细胞中突触兴奋和抑制的比例保持不变。光刺激海马传入的BNST和PVN在体内抑制急性束缚应激产生的血液糖皮质激素水平的上升。因此，我们提供的功能证据表明，海马向BNST的输出有助于下丘脑-垂体轴的净抑制，从而使用具有增强空间和时间分辨率的方法对这一过程提供了进一步的机制见解。
The hippocampus exerts inhibitory feedback on the release of glucocorticoids. Because the major hippocampal efferent projections are excitatory, it has been hypothesized that this inhibition is mediated by populations of inhibitory neurons in the hypothalamus or elsewhere. These regions would be excited by hippocampal efferents and project to corticotropin-releasing factor (CRF) cells in the paraventricular nucleus of the hypothalamus (PVN). A direct demonstration of the synaptic responses elicited by hippocampal outputs in PVN cells or upstream GABAergic interneurons has not been provided previously. Here, we used viral vectors to express channelrhodopsin (ChR) and enhanced yellow fluorescent protein (EYFP) in pyramidal cells in the ventral hippocampus (vHip) in mice expressing tdTomato in GABA- or CRF-expressing neurons. We observed dense innervation of the bed nucleus of the stria terminalis (BNST) by labeled vHip axons and sparse labeling within the PVN. Using whole-cell voltage-clamp recording in parasagittal brain slices containing the BNST and PVN, photostimulation of vHip terminals elicited rapid excitatory postsynaptic currents (EPSCs) and longer-latency inhibitory postsynaptic currents (IPSCs) in both CRF+ and GAD + cells. The ratio of synaptic excitation and inhibition was maintained in CRF + cells during 20 Hz stimulus trains. Photostimulation of hippocampal afferents to the BNST and PVN in vivo inhibited the rise in blood glucocorticoid levels produced by acute restraint stress. We thus provide functional evidence suggesting that hippocampal output to the BNST contributes to a net inhibition of the hypothalamic-pituitary axis, providing further mechanistic insights into this process using methods with enhanced spatial and temporal resolution.
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