INVESTIGATING CELLULAR AND CIRCUIT DEVELOPMENT OF BNST CAMKII NEURONS IN A MOUSE MODEL OF TOURETTE’S SYNDROME

Tourette’s syndrome (TS) comorbid with obsessive-compulsive disorder (OCD) is a neurodevelopmental disorder affecting approximately 1 in 160 people. Although its etiology remains incompletely understood, some severe cases of TS have been linked to mutations in the Hdc gene, encoding for the enzyme responsible for histamine synthesis, with patients carrying this mutation exhibiting lowered histamine levels. While TS and OCD are traditionally viewed as disorders of the basal ganglia, both disorders show a strong social component, where stress and anxiety exacerbate tic expression. The bed nucleus of the stria terminalis (BNST) is a key brain region in regulating stress and anxiety that interacts with the basal ganglia and is heavily innervated by histaminergic afferents during early postnatal periods (Marquez-Gomez et al. 2026). We therefore hypothesize that BNST development might be critical in the emergence of TS with OCD symptoms and is that it is altered by reduced histamine levels. To investigate this, we characterized a distinct subpopulation of glutamatergic BNST neurons expressing Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) using a combination of electrophysiology, immunohistochemistry and synaptic tracing to explore how altered histamine levels impact their development and circuit integration. We find that CaMKII neurons are an electrophysiologically distinct population of neurons within the BNST and that changing histamine levels can alter their development as well as their synaptic connectivity. These findings demonstrate that perinatal histamine dysregulation impacts BNST development and might contribute to stress and anxiety induced exacerbation of tic expression in TS.