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Neuron. 2015 Mar 18;85(6):1344-58. doi: 10.1016/j.neuron.2014.12.025. Epub 2015 Mar 5.

Collateral pathways from the ventromedial hypothalamus mediate defensive behaviors.

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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. Electronic address:


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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