PoMAM · ENGRAMS IN TRAUMATIC MEMORY: FINDING NOVEL THERAPEUTIC AVENUES IN DEPRESSION AND PTSD.

Despite 70% of people are going to experience a traumatic event throughout life, only 3.9% are going to develop post-traumatic stress disorder (PTSD). Curiously, people who develop PTSD also present a higher risk of developing Major Depressive Disorder (MDD). Thus, 50-70% of PTSD patients will live with a diagnostic of MDD, which in terms of prognosis means poor response to treatment and worse symptomatology. Despite the clinical relevance of this comorbidity, it remains unknown if there are shared molecular mechanisms. Impairments in fear memory and learning were related to PTSD and MDD, in association with atrophy and synaptic loss in the hippocampus (HPC). In turn, the HPC plays a crucial role in fear memory, encoding the contextual information related to the fearful stimulus. Thus, we propose that maladaptive fear memory due to hippocampal dysfunction can also contribute to MDD, explaining the high co-morbidity between PTSD and MDD. Importantly, preclinical research focus on fear memory have provided us with promising knowledge for potential PTSD therapeutics. For instance, the regulation of glucocorticoids in the golden hours after trauma to prevent memory consolidation, the use of beta-adrenergic blockers to disrupt consolidated memories, or different psychotherapeutic approaches to enhanced memory extinction. Recently, the advances with chemo- and optogenetic technics have allowed the identification and functional modulation of neurons involved in encoding a specific memory (engrams), thereby allowing a highly refined study of memory substrates. Despite these advances, the use of such approaches in genetic animal models for the study of psychiatric comorbidities is still poorly explored. We believe that this combination can bring new insights and methodological possibilities for the field. In parallel, increase our understanding about the basis of PTSD and MDD can provide new therapeutical targets with direct implications for human health.