Synaptic connectome maladaptation in the circuits of innate fear

Mental disorders account for 30% of the global disease burden. Anxiety disorders represent the highest proportion with conditions such as post-traumatic stress disorder (PTSD). Women are twice as likely to develop PTSD compared to men. Importantly, only a susceptible subpopulation of stressed individuals develops PTSD.

Despite the identification of affected brain regions (e.g. hypothalamus, amygdala, periaqueductal gray), critical neuronal types, and their disbalanced circuit connectivity resulting in maladaptation are poorly understood.The sense of smell can contribute to induce PTSD. War Veterans with PTSD were distressed by the smell of burning rubber.

We use all-optical voltage imaging ex vivo and in vivo and spatial transcriptomics to investigate maladapted and resilient neuronal connectomes of hypothalamic and periaqueductal circuits in olfactory predator stress model of PTSD.

We aim to identify critical circuit motifs that underlie the susceptibility to develop PTSD-like state both in female and male mice to uncover sex-specific sensitivity resulting in the prevalence of PTSD in women.In summary, this research will explore genetically- and anatomically defined maladapted neuronal circuits ex vivo and in vivo to identify critical circuit motifs that predict susceptibility and development of long-lasting PTSD-like state.

The intended research has high potential to reveal genetic therapeutic targets and strategies to reverse the circuit imbalance in PTSD.