Prior daily practice of a sustained attention task during the light phase evokes a diurnal behavioral activity pattern and a task time-synchronized increase in prefrontal cholinergic neurotransmission

We recently observed that daily practice of a sustained attention task (SAT) during the light phase of the light/dark cycle causes a stable, entrained, diurnal behavioral activity pattern (Gritton et al. 2009). As SAT performance increases cortical acetylcholine (ACh) release, this experiment assessed the influence of the prefrontal ACh on SAT practice-induced diurnality. Circadian behavioral activity was recorded to verify the SAT effect on circadian activity, and prefrontal ACh release was measured, using microdialysis, 3 days following the last practice session. SAT practice occurred either during the light phase [ZT4] or during the dark phase, [ZT16]. A control group practiced a daily fixed interval 9 s [FI-9] schedule of reinforcement at ZT4. A second control group was handled at randomly selected times but was neither water-deprived nor performed a task [NP]. Dialysates were collected every 15 min for 180 min total, beginning 90 min before the prior onset of task practice and again during the equivalent time period twelve hours later. For all animals, ACh release was higher during the dark phase when compared with the light period. Furthermore, in previously SAT-performing animals, ACh levels increased for 45 min at ZT4 and ZT16. Collectively these results indicate that the diurnal activity pattern that results from SAT practice during the light phase is not mediated via global alterations in the circadian regulation of ACh release. However, prior practice of the SAT established a stable increase in ACh release that lasted as long as the prior SAT sessions, and this task time-synchronized increase in prefrontal cholinergic activity may contribute to the induction or maintenance of diurnality in ZT4 animals. Future research is testing whether removal of cholinergic neurons interferes with ZT4 SAT practice-induced diurnality. Furthermore, it will be important to determine the time point after cessation of SAT practice at which ZT4 animals reverse to a nocturnal pattern and whether this coincides with the loss of task time-synchronized cholinergic activity. This research provides new insights in understanding cognitive work-induced shifts in circadian rhythms, the cause and role of circadian abnormalities in neuropsychiatric disorders, and it eventually will inform the development of treatments of such disorders.