Post-traumatic stress disorder (PTSD) is a chronic disorder that develops in vulnerable people after trauma. It has been estimated that 50% of the world population will experience a traumatic event in their lifetime. Even if subjects experiencing a traumatic event all show an acute response to the trauma, only a subset of them (susceptible) ultimately develops PTSD, meanwhile the others (resilient) fully recover after an acute response. Animal models of PTSD lack of a dynamic dissection to understand how this acute response can turn into PTSD-related maladaptive changes in susceptible individuals.
The basolateral amygdala (BLA) plays a crucial role in the modulation of traumatic memories, and, the stimulation of presynaptic inputs from the BLA to the infralimbic prefrontal cortex (IL) enhances extinction of fear memory. Furthermore, there is evidence showing that variations in the gut microbiota has an important role in the development of mood disorders, such as PTSD.
The present project has a dual aim that will be addressed in rats stratified with respect to susceptibility or resiliency towards the development of a chronic PTSD-like phenotype after trauma.
In the aim 1a we will investigate if by boosting or blocking the endocannabinoid signaling in the BLA of resilient and susceptible rats, respectively, the fear memory extinction process could be enhanced, converting a resilient in a susceptible PTSD-like phenotype, or viceversa.
In the aim 1b we will investigate if by stimulating or inhibiting the presynaptic inputs from the BLA to the infralimbic cortex (IL) in resilient and susceptible rats, respectively, the fear memory extinction process is enhanced, converting a resilient in a susceptible PTSD-like phenotype or viceversa.
In aim 2 we will investigate the role of the gut microbiota on PTSD susceptibility and resiliency.
On the whole, this project will offer new hints for innovative therapeutic approaches in PTSD.
The completion of this project is bound to significantly advance the knowledge of memory processes in general and, importantly, when trauma experience generates behavioral pathology as in PTSD. The completion of this project will open new lines of high translational research, as we will comprehensively investigate the trauma inducing phenotypes of the PTSD with novel and advanced techniques, such as optogenetic, for detection of novel therapeutic target by widely investigating on changes in brain areas and circuit in a PTSD-like phenotype specific manner. This project will provide the research and medical community innovative points of view to treat and perhaps even cure PTSD, indeed, in the second aim we will consider the microbiota alterations in PTSD-like susceptible rats providing an innovative therapeutic target to counteract PTSD in most of its features. We are confident that our work will open venues for novel therapeutic strategies than can be commercially exploited in the future.