Szebik, H. | Search bioRxiv

bioRxiv2024

Pretrauma cognitive traits predict trauma-induced fear generalization and associated prefrontal functioning in a longitudinal model of posttraumatic stress disorder

Posttraumatic stress disorder (PTSD) is a chronic psychiatric condition that develops in susceptible individuals exposed to traumatic stress, challenging clinicians to identify risk factors and mechanisms for mitigating vulnerability. Here we investigated behavioral predictors of high fear generalization, a core PTSD symptom, and its neural correlates longitudinally in rats. In a comprehensive behavioral test battery of emotional and cognitive function, pretrauma lower operant learning performance emerged as high predictor of fear generalization following trauma. Posttrauma operant training facilitated fear extinction, suggesting an overlap in neural circuits governing operant learning and fear expression. Neuronal activity mapping revealed significant changes in the medial prefrontal cortex (mPFC) in high fear generalizers, with alterations in CRH/VIP+ interneuron functioning. Silencing prefrontal Crh expression after fear memory consolidation enhanced mPFC activation and reduced fear expression, favoring resilience. These findings highlight operant learning and mPFC alterations as vulnerability markers and mediators of excessive fear generalization, with implications for prevention and targeted therapy in PTSD.

neuroscience↗

bioRxiv2020

Somatostatin neurons of the bed nucleus of stria terminalis enhance associative fear memory consolidation in mice

Excessive fear learning and extinction-resistant fear memories are core symptoms of anxiety and trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity of the bed nucleus of stria terminalis (BNST) under these conditions, the role of BNST in fear learning and expression is still not clarified. Here, we tested how BNST modulates fear learning in mice using a chemogenetic approach. Activation of GABAergic neurons of BNST during fear acquisition, more specifically the consolidation phase, resulted in enhanced cued fear recall. Importantly, BNST activation had no acute impact on fear expression during conditioning or recalls, but it enhanced cued fear recall subsequently, potentially via altered activity of downstream regions as indicated by c-Fos. Enhanced fear memory consolidation could be replicated by selectively activating somatostatin neurons (but not corticotropin releasing factor neurons), suggesting significant modulation of fear memory strength by specific circuits of BNST.

neuroscience↗