Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Neuroscience Institute, New York University School of Medicine, New York, NY, USA.
Nat Neurosci. 2019 Apr;22(4):576-585. doi: 10.1038/s41593-019-0342-2. Epub 2019 Mar 4.
Corticotropin-releasing factor (CRF) that is released from the paraventricular nucleus (PVN) of the hypothalamus is essential for mediating stress response by activating the hypothalamic-pituitary-adrenal axis. CRF-releasing PVN neurons receive inputs from multiple brain regions that convey stressful events, but their neuronal dynamics on the timescale of behavior remain unknown. Here, our recordings of PVN CRF neuronal activity in freely behaving mice revealed that CRF neurons are activated immediately by a range of aversive stimuli. By contrast, CRF neuronal activity starts to drop within a second of exposure to appetitive stimuli. Optogenetic activation or inhibition of PVN CRF neurons was sufficient to induce a conditioned place aversion or preference, respectively. Furthermore, conditioned place aversion or preference induced by natural stimuli was significantly decreased by manipulating PVN CRF neuronal activity. Together, these findings suggest that the rapid, biphasic responses of PVN CRF neurons encode the positive and negative valences of stimuli.
促肾上腺皮质释放因子（CRF）由下丘脑的室旁核（PVN）释放，对于通过激活下丘脑-垂体-肾上腺轴来介导应激反应是必不可少的。CRF 释放的 PVN 神经元接收来自多个传达应激事件的脑区的输入，但它们在行为时间尺度上的神经元动力学仍然未知。在这里，我们对自由活动的小鼠的 PVN CRF 神经元活动进行了记录，结果表明，CRF 神经元会立即被一系列厌恶性刺激激活。相比之下，在接触到食欲性刺激的一秒内，CRF 神经元的活动开始下降。光遗传激活或抑制 PVN CRF 神经元足以分别诱导条件性位置厌恶或偏好。此外，通过操纵 PVN CRF 神经元活动，可显著降低由自然刺激引起的条件性位置厌恶或偏好。总的来说，这些发现表明，PVN CRF 神经元的快速双相反应编码了刺激的正性和负性效价。
