Attentional deficits are prevalent and persistent after traumatic brain injury (TBI), yet our understanding of their etiology is incomplete. In uninjured rats, in vivo microdialysis studies show that task-evoked increases in acetylcholine (ACh) in the medial prefrontal cortex (mPFC) correlate with enhanced attentional performance. The goal of this study was to test the hypothesis that TBI decreases task-evoked ACh in the mPFC, compromises nucleus basalis of Meynert (nbM) cholinergic neuron morphology, and impairs attention. Adult male Sprague-Dawley rats trained on the three-choice serial reaction time (3-CSRT) task and then received either a controlled cortical impact or sham injury (n = 10/group). Dialysate samples were collected by in vivo microdialysis before and during the 3-CSRT task, and ACh levels were quantified using high-performance liquid chromatography. Cholinergic neurons in the contralateral/ipsilateral nbM were reconstructed and analyzed using the IMARIS software. The findings revealed a task-evoked decrease in ACh in the TBI group, a significant reduction in soma area/volume in the ipsilateral nbM, and impaired sustained attention as measured by performance on the 3-CSRT task. The findings support the hypothesis that TBI-induced attentional impairments are linked to disrupted real-time cholinergic signaling in the mPFC and associated structural changes in cholinergic neurons. These insights could inform the development of targeted interventions to improve quality of life for TBI survivors.
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