Background: Cholinergic signalling to the prefrontal cortex (PFC) plays a critical role in attention and memory, with damage to either resulting in dementia or impaired stroke recovery. Use of nicotinic alpha-seven agonists, such as PHA568487, improves memory and stroke recovery, however, the efficacy of starting the treatment early versus late remains unknown. Aim: We investigated whether attention was impaired following stroke to the PFC using the five-choice serial reaction time task (5-CSRTT) and whether treatment with PHA568487 ameliorated this impairment. Methods: Nine month male C56BL/6J mice were assigned a treatment groups (sham-saline, stroke-saline, stroke + PHA568487 early (three-days post-stroke) and stroke + PHA568487 late (three-weeks post-stroke)) based on learning rates in the 5-CSRTT (N=11-16 per group). Focal stroke to the PFC was induced using the photothrombosis method.  Animals received daily intraperitoneal injections of 0.8mg/kg PHA568487 in saline. From 3.5 weeks post-stroke, animals were tested on attentional probes by altering the inter-trial interval (ITI) or stimulus duration and data compared using pairwise comparisons. Results: Compared to shams, stroke animals showed impairments in the ITI (correct responses and omissions; P<0.05) and stimulus duration probe (correct responses; P<0.05). Treatment with either early or late PHA568487 showed no significant differences in both ITI and stimulus duration probes compared to stroke controls (P>0.05). Conclusions: Stroke to the PFC results in impaired attention on the 5-CSRTT that was not ameliorated following treatment with PHA568487. By better understanding how stroke influences attentional and other memory deficits, we will be able to investigate potential therapies for clinical use.

STROKE TO THE PREFRONTAL CORTEX DISRUPTS CHOLINERGIC SIGNALLING AND IMPAIRS ATTENTION