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Wang, Li; Chen, Irene Z.; Lin, Dayu
Neuron (Cambridge, Mass.), 03/2015, Volume: 85, Issue: 6Journal Article
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. •Activating VMHdm/c SF1 cells induces defensive-like motor and autonomic responses•The VMH→PAG and VMH→AHN pathways mediate immobility and avoidance, respectively•VMHdm/c neurons send collateral projections to the AHN and dlPAG•AHN activation elicits escape jumping and avoidance, but not immobility Wang et al. show that SF1-expressing cells in the ventromedial hypothalamus (VMH) mediate complex defense-like somatomotor and autonomic responses. Collateral projections from the VMH to different downstream regions mediate distinct aspects of defense, suggesting a one-to-many and nonredundant circuit configuration.
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