A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response.
A common substrate for prefrontal and hippocampal inhibition of the neuroendocrine stress response.
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DOI：
10.1523/jneurosci.6040-10.2011
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发表时间：
2011-06-29
期刊：
影响因子：
--
通讯作者：
Sawchenko PE
中科院分区：
文献类型：
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作者：
Radley JJ;Sawchenko PE
边缘前脑细胞群的相互连接网络，包括内侧前额叶皮质（mPFC）和海马结构（HF），已知对情绪压力体验的适应性反应，包括下丘脑-垂体-肾上腺（HPA）轴的输出。虽然边缘系统HPA抑制系统的破坏与压力相关的精神病和全身性疾病有关，但由于缺乏对提供这种调节的组织的系统水平的理解，该领域的进展受到阻碍。使用大鼠，我们首先本地化的细胞群传入的下丘脑室旁核（PVH，发起人HPA反应的压力），其参与后急性（30分钟）限制减少了兴奋性毒素病变的腹侧下托，HF的一个组成部分。这确定了一个候选继电器给予HF的影响，在一个有限的部分前床核的终纹（aBST），我们以前确定为GABA能继电器subserving mPFC抑制的应力轴。解剖跟踪实验表明，外在的预测从HF和mPFC收敛到aBST的区域，包含神经元，都是压力敏感和PVH的投射。最后两个实验提供的证据表明：（1）mPFC和HF的HPA抑制影响是相加的，（2）aBST比vSUB对应激诱导的HPA终点发挥更突出的抑制作用。这些研究结果支持这样的观点，即mPFC和HF的应激抑制影响主要是通过会聚到一个共同的中继，而不是一个串行，并行或更复杂的多突触网络。
A network of interconnected limbic forebrain cell groups, including the medial prefrontal cortex (mPFC) and hippocampal formation (HF), is known to shape adaptive responses to emotionally stressful experiences, including output of the hypothalamo-pituitary-adrenal (HPA) axis. While disruption of limbic HPA-inhibitory systems is implicated in stress-related psychiatric and systemic illnesses, progress in the field has been hampered by a lack of a systems level understanding of the organization that provides for this regulation. Using rats, we first localized cell groups afferent to the paraventricular hypothalamic nucleus (PVH, the initiator of HPA responses to stress) whose engagement following acute (30 min) restraint was diminished by excitotoxin lesions of the ventral subiculum, a component of the HF. This identified a candidate relay for imparting HF influences in a circumscribed portion of the anterior bed nucleus of the stria terminalis (aBST), which we previously identified as a GABAergic relay subserving mPFC inhibition of the stress axis. Anatomical tracing experiments then indicated that extrinsic projections from HF and mPFC converge onto regions of aBST that contain neurons that are both stress-sensitive and PVH-projecting. Two final experiments provided evidence that (1) HPA-inhibitory influences of mPFC and HF are additive, and (2), that aBST plays a more prominent inhibitory role than vSUB over stress-induced HPA endpoints. These findings support the view that stress-inhibitory influences of mPFC and HF are exerted principally via convergence onto a common relay, as opposed to a serial, parallel or more complex multisynaptic network.