Scientific Rationale

The research underlyling the current PTSD investigations at Neurovation Labs utilized a robust model of PTSD in rodents called stress-enhanced fear learning (SEFL). In the SEFL model, an acute, severe, and unpredictable stressor permanently sensitizes conditional fear learning. Rats are given 15 unsignaled footshocks in a certain context (the “trauma” context) and some time later are given a single footshock in a novel context (the “reminder” context). When rats are tested for changes in freezing levels (i.e., fear levels) in the formerly novel context in absence of a shock, they show exaggerated levels of freezing behavior, This is called SEFL. This is analogous to a scenario where a soldier who has returned home from active duty experiences a major fear reaction in response to hearing a car backfire, for instance.  This is the crux of PTSD symptomatology and what SEFL accomplishes in a rodent model.

SEFL is a unique PTSD model in that it combines both non-associative and associative learning techniques (please see our FAQs page for a detailed explanation on the different types of learning). Because of this, it is able to capture multiple aspects of PTSD, including exaggerated fear, as seen through freezing, and blunted emotional reactivity, as measured through reactivity to the shock (we focus on the former aspect as a tractable measure of fear). These animal studies also show dysregulated HPA axis activation can enhance fear responding, and their results are consistent with the stress response of PTSD patients. Rats exhibiting SEFL further show anxiety behavior in open fields and elevated plus maze tests (i.e., overall anxiety), increased consumption of alcohol, potentiated startle reactivity (i.e., startle response), and a depression-like phenotype in a forced swim test.

Dr. Perusini together with Dr. Fanselow determined the mechanisms underlying both the induction and expression of SEFL. They found that corticosterone, or cortisol in humans, is necessary for SEFL to occur, and it in part increases GluA1 levels in the basolateral amygdala (BLA), the fear center of the brain, long-after the traumatic experience. Neurovation Labs has built on these discoveries to develop the first true diagnostic and companion treatment for PTSD and other anxiety and stress disorders.

Perusini, et al. 2015