Astroglial Perisynaptic Plasticity and Glutamate Uptake in a Contextual Fear Conditioning Paradigm

Post-traumatic stress disorder (PTSD) is one of the most prevalent psychiatric disorders worldwide and is characterized by exaggerated threat responses to both trauma-related and trauma-unrelated cues. Morphological and functional alterations in astrocytes contribute to the pathophysiology of PTSD, including changes in the perisynaptic proximity of GLT-1. The expression profiles of GLT-1, GFAP, and Ezrin were analyzed in brain regions critically involved in anxiety and fear processing, including the amygdalar nuclei (BLA and CeA), the bed nucleus of the stria terminalis (BNST), and the dorsal hippocampus (HPC), using a classical contextual fear-conditioning (CFC) paradigm to model alterations relevant to PTSD. CFC is a well-established animal model for studying associative threat memory. In PTSD, threat memories display pathological features—including hypermnesia, overgeneralization, and deficits in extinction and extinction retention—that distinguish them from non-pathological memories. CFC was performed in male and female mice using footshock intensities of 0.10 mA and 0.60 mA, operationalized to model low- and high-threat conditions, respectively. The perisynaptic plasticity induced by the CFC protocol may alter glutamate concentrations within the synaptic cleft, thereby contributing to the molecular and cellular processes underlying the behavioral alterations characteristic of PTSD.