IMPACT OF ADVERSE EXPERIENCES IN EARLY LIFE ON THALAMIC NEURAL CIRCUITS

Structural and functional alterations in different regions of the CNS are implicated in the etiopathology of psychiatric disorders. Early life stress (ELS) is a known risk factor for developing such disorders through the induction of changes in the CNS. Parvalbumin (PV) positive neurons, glial cells and plasticity-related molecules are most affected by this ELS and psychiatric disorders. Previous studies reported abnormalities in these components in different brain regions, especially in corticolimbic structures, on which most studies have traditionally focused, given their roles in cognition. However, the thalamus remains largely unexplored despite its role as a critical relay that interconnects these regions and its prolonged postnatal development, which may confer vulnerability to ELS. This study aimed to investigate possible alterations in the mediodorsal thalamic nucleus (MD) because of its high connectivity with the prefrontal cortex and its vulnerability in different psychiatric disorders. A peripubertal stress (PPS) mouse model was employed to analyze long-lasting changes induced by ELS on PV+ puncta and their interactions with microglia in the MD of female and male mice. Significant alterations in the mean fluorescence intensity and area occupied by PV+ puncta were observed only in the lateral MD of stressed females. These findings suggest that ELS can induce region- and sex-specific alterations in thalamic circuitry. Future studies will examine potential changes affecting other plasticity-related molecules in this PPS model. Moreover, human postmortem studies will be performed to investigate alterations in similar markers in samples of individuals with bipolar disorder, depression, and schizophrenia.