All-optical Dissection of Hypothalamic and Periaqueductal Inhibitory Circuits of Female Panic Disorder

Panic disorder (PD) has 2.5 times higher prevalence in women than in men.

To develop effective treatment strategies for PD, it is crucial to examine the pathophysiology of brain circuits that are underlying the development of PD.

Our research aims to investigate differences of circuit changes in female and male mice in panic-like states, which is of great translational value since the neurobiology underlying sex-difference in PD remains poorly understood at the circuit level.The periaqueductal gray matter (PAG) is critical for processing panicogenic stimuli.

The anterior hypothalamic nucleus (AHN) responds to threats such as the proximity of predators.

The ventromedial hypothalamus (VMH) induces defensive and panic-like behaviors in rodents and panic seizures in human patients. The VMH provides monosynaptic excitatory input both to PAG and to the AHN.

The organization of defense reactions in the PAG utilizes inhibitory transmission, and the AHN consists of inhibitory neurons in 90%.

However, the identity of the VMH-driven PAG and AHN neurons and the circuit motifs that process panic-related information from is poorly understood.In this research I propose to determine the key role of distinct inhibitory populations and circuit motifs of the VMH-PAG and VMH-AHN pathways in the development of panic-like state in male and female mice.

The intended research has a high potential to reveal new genetic therapeutic targets and strategies to reverse the circuit imbalance in female PD.