Bi-directional Interactions between Cognition and Circadian Rhythms.

Abstract

Circadian rhythms are ubiquitous and dynamic, allowing organisms to adapt and anticipate key environmental cues under a variety of conditions. Circadian systems are also complex regulatory mechanisms, involving the synchronization and coherent activity of many individual oscillators to maintain normal function. The loss of coherence amongst individual oscillators, characteristic of shift-work and some neuropsychiatric illnesses, results in a state of internal desynchrony that has been proposed to impact human health and productivity. Research described in this dissertation focuses on the interaction between forebrain cholinergic signaling and circadian rhythms. Furthermore, this research presents an animal model that forms the basis for studying the risk of prolonged shift-work on cognitive performance and physiological wellbeing.

While a variety of environmental cues are able to influence circadian rhythms, relatively little is known about how this modulation occurs or the mechanisms that underlie entrainment. Data demonstrated that cholinergic neurotransmission in the suprachiasmatic nucleus (SCN) acts as a prominent non-photic entrainment signal that alters circadian timing during tasks requiring sustained attentional effort. Changes in entrainment were strongly correlated with conditions where performance demands taxed the cognitive control of attention. Surprisingly, cognitive activity alone is capable of entraining circadian rhythms in animals lacking a functional SCN. However, SCN-lesioned animals also exhibit significant impairments in cognitive performance suggesting SCN function is important for cognitive learning.

The data also reveal that circadian processes interact with learning and memory consolidation in a bidirectional manner, particularly for tasks requiring attentional effort. Nocturnal rodents demonstrate better acquisition and performance when trained during the dark-phase as compared to daytime trained animals.

Collectively, these results illustrate that cholinergic signaling influences entrainment through interactions with the SCN and still unidentified oscillators outside of the SCN. Further, circadian rhythmcity can be modified through adaptive processes in the service of cognitive performance. These findings reveal that multiple clocks co-exist in the CNS and compete for control of circadian output. Animal models are important for understanding the mechanisms that lead to disruption of circadian oscillators and the testing of putative treatments to attenuate or prevent circadian desynchronies commonly present in shift-workers, the aging population, and some neuropsychiatric disorders.