We recently observed that performance of a cognitive task (specifically an attention-demanding task, not involving stressors or unexpected events and not requiring noradrenergic activation), declined during recovery from a phase-shift of the light cycle. Furthermore, stable circadian activity patterns were radically altered by daily training on such a task during the subjective rest phase (i.e., rats became day active). As performance on this task depends upon the integrity and activity of the basal forebrain - cortical cholinergic input system, and as activity in this system during performance is controlled by top-down prefrontal regions, the main goal of the proposed research is to determine the neuronal mechanisms allowing cognition- associated cholinergic activity to modulate circadian rhythms. Although the HPA axis and central attention mechanisms interact, the impact of bottom-up and top-down arousal mechanisms on circadian rhythms appears to be quite different. We hypothesize that the effects of cognitive activity on circadian rhythms are mediated via activation of basal forebrain cholinergic projections to the SCN, while stimulation of the HPA axis contributes little to the reorganization of cognition-entrained rhythms.
Specific Aim 1 tests the hypothesis that bottom-up, HPA-mediated arousal is not sufficient or necessary for entraining activity during the rest phase. We will test the hypothesis by examining changes in corticosterone release and ACh release following entrainment to a non-photic signal during the day, while intact or after adrenalectomy or basal forebrain lesions.
Specific Aim 2 tests the hypothesis that the pattern of circadian re-organization caused by performance of an attention-demanding cognitive task is gradual, learning-related, and time-of-day specific.
Specific Aim 3 tests the hypothesis that basal forebrain cholinergic efferents to the SCN are necessary for the effects of attention-demanding cognition on circadian entrainment. Results from these experiments may increase our understanding of circadian changes associated with shift work, Alzheimer's disease, depression and bipolar disorder. Potential treatments for such disorders may include manipulation of the cortical cholinergic system control of circadian entrainment.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Biological Rhythms and Sleep Study Section (BRS)
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Vicentic, Aleksandra
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University of Michigan Ann Arbor
Schools of Arts and Sciences
Ann Arbor
United States
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Gritton, Howard J; Stasiak, Ashley M; Sarter, Martin et al. (2013) Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms. PLoS One 8:e56206
Gritton, Howard J; Kantorowski, Ana; Sarter, Martin et al. (2012) Bidirectional interactions between circadian entrainment and cognitive performance. Learn Mem 19:126-41
Paolone, Giovanna; Lee, Theresa M; Sarter, Martin (2012) Time to pay attention: attentional performance time-stamped prefrontal cholinergic activation, diurnality, and performance. J Neurosci 32:12115-28
Gritton, Howard J; Sutton, Blair C; Martinez, Vicente et al. (2009) Interactions between cognition and circadian rhythms: attentional demands modify circadian entrainment. Behav Neurosci 123:937-48