Investigation of the neuronal ensembles and molecular mechanisms underpinning observational fear memory

Anxiety disorders are characterized by aberrant processing of fearful memories. Substantial evidence indicates that socially transmitted fear can promote anxiety disorders. However, the understanding of the underlying neurobiological mechanisms remains limited.

Here, I propose to investigate the neuronal ensembles and molecular mechanisms that promote observational fear (i.e., socially transmitted fear) by using a multidisciplinary approach that combines translational animal models with state-of-the-art viral vector and RNA sequencing approaches. Observational and direct fear memories have partly shared neural mechanisms.

I recently found that the epigenetic enzyme PRDM2 regulates fear memory after exposure to direct threats.

In Aim 1, I will determine whether dysregulation of PRDM2 is a shared mechanism that contributes to maladaptive fear memory during both direct and observational fear.

In Aim 2, I will take on a discovery approach to identify previously unknown neurobiological substrates of observational fear using a whole brain activity mapping approach.

Finally in Aim 3, I will assess fear-associated transcriptomic reprogramming within the neuronal ensembles identified in Aim 2.

Understanding the neurobiological basis of observational fear will provide insights on maladaptive fear response and provide novel therapeutic targets for anxiety disorders. This is a 5-year project that includes the participation of 1 graduate student, 1 postdoc, 2 guest researchers and me.