Wang Li, Chen Irene Z, Lin Dayu
Institute of Neuroscience, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA.
Institute of Neuroscience, New York University School of Medicine, 522 First Avenue, New York, NY 10016, USA; Department of Psychiatry, New York University School of Medicine, 1 Park Avenue, New York, NY 10016, USA; Center for Neural Science, New York University, 4 Washington Place, New York, NY 10003, USA; The Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA.
Neuron. 2015 Mar 18;85(6):1344-58. doi: 10.1016/j.neuron.2014.12.025. Epub 2015 Mar 5.
The ventromedial hypothalamus (VMH) was thought to be essential for coping with threat, although its circuit mechanism remains unclear. To investigate this, we optogenetically activated steroidogenic factor 1 (SF1)-expressing neurons in the dorsomedial and central parts of the VMH (VMHdm/c), and observed a range of context-dependent somatomotor and autonomic responses resembling animals' natural defensive behaviors. By activating independent pathways emanating from the VMHdm/c, we demonstrated that VMHdm/c projection to the dorsolateral periaqueductal gray (dlPAG) induces inflexible immobility, while the VMHdm/c to anterior hypothalamic nucleus (AHN) pathway promotes avoidance. Consistent with the behavior changes induced by VMH to AHN pathway activation, direct activation of the AHN elicited avoidance and escape jumping, but not immobility. Retrograde tracing studies revealed that nearly 50% of PAG-projecting VMHdm/c neurons send collateral projection to the AHN and vice versa. Thus, VMHdm/c neurons employ a one-to-many wiring configuration to orchestrate multiple aspects of defensive behaviors.
腹内侧下丘脑(VMH)被认为在应对威胁时至关重要,尽管其神经回路机制尚不清楚。为了对此进行研究,我们采用光遗传学方法激活VMH背内侧和中央部分(VMHdm/c)中表达类固醇生成因子1(SF1)的神经元,并观察到一系列依赖于环境的躯体运动和自主反应,类似于动物的自然防御行为。通过激活源自VMHdm/c的独立通路,我们证明VMHdm/c向背外侧导水管周围灰质(dlPAG)的投射会诱导僵硬的不动状态,而VMHdm/c到下丘脑前核(AHN)的通路则促进回避行为。与VMH到AHN通路激活所诱导的行为变化一致,直接激活AHN会引发回避和逃避跳跃,但不会导致不动状态。逆行追踪研究表明,近50%投射到PAG的VMHdm/c神经元会向AHN发出侧支投射,反之亦然。因此,VMHdm/c神经元采用一对多的布线配置来协调防御行为的多个方面。