Collateral pathways from the ventromedial hypothalamus mediate defensive behaviors.

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Neurobiology

Background:

• The ventromedial hypothalamus (VMH) is implicated in threat response, but its precise neural circuitry is not fully understood.
• Understanding the neural basis of defensive behaviors is crucial for comprehending threat perception and coping mechanisms.

Purpose of the Study:

• To elucidate the circuit mechanisms by which the ventromedial hypothalamus (VMH) controls defensive behaviors.
• To investigate the role of steroidogenic factor 1 (SF1)-expressing neurons within the VMH in orchestrating somatomotor and autonomic responses.

Main Methods:

• Optogenetic activation of SF1-expressing neurons in the VMHdm/c.
• Selective activation of VMHdm/c projection pathways to the dorsolateral periaqueductal gray (dlPAG) and anterior hypothalamic nucleus (AHN).
• Retrograde tracing to identify neuronal projections and collateralization.

Main Results:

• Activation of VMHdm/c to dlPAG pathway induced inflexible immobility.
• Activation of VMHdm/c to AHN pathway promoted avoidance and escape jumping.
• AHN activation alone elicited avoidance, but not immobility.
• Significant collateral projections were observed between VMHdm/c, dlPAG, and AHN.

Conclusions:

• VMHdm/c neurons utilize a one-to-many wiring strategy to control diverse defensive behaviors.
• Distinct VMHdm/c pathways differentially regulate immobility and avoidance responses.
• The VMH-AHN pathway is critical for promoting avoidance behaviors during threat.
• The VMH-dlPAG pathway is essential for inducing immobility as a defensive strategy.