Neuron
Volume 85, Issue 6, 18 March 2015, Pages 1344-1358
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Article
Collateral Pathways from the Ventromedial Hypothalamus Mediate Defensive Behaviors

https://doi.org/10.1016/j.neuron.2014.12.025Get rights and content
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Highlights

  • 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

Summary

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.

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