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Completed RESEARCH GRANT UKRI Gateway to Research

Chronotype and circadian reafference: the impact of free will on the mammalian circadian clock

£6.5M GBP

Funder Biotechnology and Biological Sciences Research Council
Recipient Organization The University of Manchester
Country United Kingdom
Start Date Aug 31, 2021
End Date Sep 29, 2025
Duration 1,490 days
Number of Grantees 2
Roles Co-Investigator; Principal Investigator
Data Source UKRI Gateway to Research
Grant ID BB/V011111/1
Grant Description

Why can't you tickle yourself? Because we experience sensations that are a product of our own actions as quite distinct from those that arise from the action of external agents. Sensations produced by ourselves are termed 'reafferent' and are a common feature of our everyday experience.

Importantly, the same sensation can have a quite different meaning if it is reafferent - when running through a forest stationary trees appear to rush towards you, distinguishing this apparent motion from the real motion of a tiger jumping out could be a matter of life and death. As a result, recognising reafferent sensations and responding accordingly is one of our brain's most important functions.

However, there is a class of reafferent sensation which presents a particular challenge because it is entirely a product of modern-day life. Access to artificial light has disrupted the previously inviolable relationship between ambient light intensity and time of day. An event (the appearance of light), that previously always signalled daytime, can now instead reflect our own actions (be reafferent).

We might wish that the brain was able to distinguish the rising sun from the light switch, but because the latter is an entirely artificial situation it cannot. An additional problem is the activities which artificial light facilitates - both arousal and exercise were previously tied to the light:dark cycle and reinforced that sense of daytime. The brain still takes them as time cues, but now their timing is often a function of our own choices.

These newly reafferent sensations impinge upon our internal biological (circadian) clock which provides an internal reflection of external time. It has been suggested that our ability to self-select the timing of light exposure and associated activities explains why there is so much variation in preferred sleep time ('chronotype') among humans. 'Larks' (early to bed, early to rise) and 'owls' (stay up late) can show very different preferences.

Fitting such divergent preferred sleep times to a uniform 9-5 work/school routine disrupts biological rhythms, the most obvious manifestation of which is so called 'social jetlag' in which owls are sleep deprived during the week and sleep in at weekends. Such disrupted rhythms impair school/work performance and contribute to widespread and intractable public health problems including mood disorders and obesity.

There is thus an urgent need to understand how reafference impacts biological clocks and what we may be able to do about it. Addressing this question in laboratory animals, in which we can achieve high control over experimental conditions and uncover mechanisms, is an important element of this endeavour. Unfortunately, common lab animals (mice and rats) do not recapitulate important aspects of reafference because they are nocturnal.

They typically avoid light, and display arousal and activity during their night-time. We have established a new laboratory rodent, the 4-striped mouse, which is strongly day active. In preparation for this proposal, we have shown that these animals can be trained to switch their lights on and off, and use this freedom to express familiar preferences - choosing bright light during the day and darkness to sleep at night.

This breakthrough provides the first opportunity to study the impact of self-selected light in lab animals. We will use the 4-striped mice to determine how daily rhythms in rest/activity are impacted by access to self-selected light and how this appears on simulated 'work' (when they are woken in the morning) and 'free' (when they can choose their own wakeup time) days.

We will establish how arousal and exercise impact rhythms by studying the part of the brain that houses the clock and by looking at how they alter rhythms in rest/activity. We will finally trial strategies for supporting good biological rhythms in the face of reafference.

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The University of Manchester

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