Disruption of basal forebrain cholinergic neurons after traumatic brain injury does not compromise environmental enrichment-mediated cognitive benefits

Abstract

Environmental enrichment (EE) attenuates traumatic brain injury (TBI)-induced loss of medial septal (MS) choline acetyltransferase (ChAT)-cells and enhances spatial learning and memory vs. standard (STD) housing. Whether basal forebrain cholinergic neurons (BFCNs) are important mediators of EE-induced benefits after TBI requires further investigation. Anesthetized female rats were randomly assigned to intraseptal infusions of the immunotoxin 192-IgG-saporin (SAP; 0.22 μg in 1.0 μL) or vehicle (VEH; 1.0 μL IgG) followed immediately by a cortical impact (2.8 mm deformation depth at 4 m/s) or sham injury and divided into EE and STD housing. Spatial learning and memory retention were assessed on post-operative days 14-19. MS ChAT⁺ cells were quantified at 3 weeks. SAP significantly reduced ChAT⁺ cells in both the EE and STD groups. Cognitive performance was improved in the EE groups, regardless of VEH or SAP infusion, vs. the STD-housed groups (p's < 0.05). No cognitive differences were revealed between the TBI + EE + SAP and TBI + EE + VEH groups (p > 0.05) or between the TBI + STD + SAP and TBI + STD + VEH groups (p > 0.05). These data show that despite significant MS ChAT⁺ cell loss, the EE-mediated benefit in cognitive recovery is not compromised.

Keywords: BFCNs, beam-walking; Behavior; Controlled cortical impact; Functional recovery; Learning and memory; Morris water maze; Traumatic brain injury.