Cognitive Performance as a Zeitgeber: Cognitive Oscillators and Cholinergic Modulation of the SCN Entrain Circadian Rhythms

Howard J Gritton,Theresa M Lee,Ashley M Stasiak,Martin Sarter,Shin Yamazaki

doi:10.1371/journal.pone.0056206

Howard J Gritton, Theresa M Lee + Show 3 more

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https://doi.org/10.1371/journal.pone.0056206

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Journal: PloS one	Publication Date: Feb 18, 2013
Citations: 77	License type: CC BY 4.0

Affiliation: University of Michigan–Ann Arbor, Michigan United

Abstract

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior.

Highlights

Circadian rhythms are shared by almost all organisms and provide a highly adaptive mechanism to anticipate daily environmental events
We quantified the thoroughness of the saporin lesions using fiber density counts of acetylcholinesterase (AChE) in the suprachiasmatic nucleus of the hypothalamus (SCN) relative to control regions
The established relationship between attentional demand, cortical acetylcholine (ACh) release, and the anatomical connectivity between cholinergic regions and the SCN led us to hypothesize that the changes in circadian entrainment associated with cognitive training are mediated through mechanisms of cholinergic signaling

Summary

Introduction

Circadian rhythms are shared by almost all organisms and provide a highly adaptive mechanism to anticipate daily environmental events. Synchronization to the LD cycle can be eliminated by bilateral ablation of the SCN [2]. Can synchronize, or entrain, to other non-photic environmental cues. Some non-photic stimuli, such as timed running wheel access and social interaction, exert their influences on behavior through phase resetting of clock genes within the SCN [3,4]. Other non-photic stimuli including fear learning, access to palatable foods, food restriction, and methamphetamine can produce entrainment even in SCN ablated animals [5,6,7,8]. Oscillators outside the SCN are necessary to entrain to these cues, recent evidence suggests that non-SCN oscillators often interact or compete with the SCN to influence biological and behavioral rhythms [9,10,11]

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