Tim talks about his lab and research into how light and the visual environment influence brain function, physiology and behaviour.

What is your research about?

My primary research interests centre on understanding the mechanisms by which light and the visual environment influence brain function, physiology and behaviour – in particular relating to visual pathways that are distinct from those responsible for conventional aspects of vision.

Accordingly, a main focus of our research is understanding the neural circuitry and sensory controls of the ‘master clock’ in the hypothalamic suprachiasmatic nuclei (SCN), which drives 24h variations in almost all aspects of physiology in line with daily changes in the external world.

In addition, however, there are several other less well studied but potentially highly influential visual pathways by which light could influence physiology, mood and cognition beyond effects on the SCN clock. Defining the sensory properties and physiological roles of those other unconventional constitutes a second key goal.

Ultimately, my goal is to use the fundamental biological insights provided by mechanistic studies in animal models to inform the use and design of lighting for humans. Indeed, here, our activities to date have already informed new international light measurement standards that take into account the unique properties of the sensory pathways that regulate the circadian system and led to the first scientific consensus guidelines for healthy lighting.

How did you enter this field of research?

My first introduction to circadian biology and electrophysiological recordings came during my MRes studies at The University of Manchester, working in the laboratory of Hugh Piggins.

I was sufficiently struck by that experience that, after completing a PhD on another interest of mine at the time (the endocannabinoid system), I returned to Hugh’s lab as a post-doc working on the understanding the roles of vasoactive intestinal polypeptide (VIP) signalling, a key regulator of clock function.

My interests in circadian biology and electrophysiology then led me take on a post-doc with Professor Rob Lucas working on the retinal mechanisms that control the circadian system, which is where my interests in the neural circuits regulating effects of light on physiology and behaviour coalesced.

In 2012, I was awarded a BBSRC David Phillips fellowship, which allowed me to form my own group to work in this area.

What approaches do you use to conduct your research?

A key and longstanding aspect of our work studying sensory coding and neural circuit function is the use of large scale multielectrode recording approaches, which allow us to record the activity of hundreds of neurons simultaneously across dispersed brain regions.

We then combine this with a range of approaches to provide causative mechanistic insights, including optogenetic tools to switch on or activate defined cell types with high spatiotemporal resolution, and carefully calibrated visual stimuli to isolate contributions from specific photoreceptive pathways.

We then build on the insights obtained by combining selective chemogenetic manipulation of the identified neural circuits with whole animal physiology and behavioural monitoring to confirm their specific roles and in circadian and light dependent biological control.

What have been the highlights of your lab’s work so far?

The role of colour signals in modulating circadian function

Traditionally, sensory control of the circadian system was thought to purely rely on the amount of environmental light. However, over the course of the day it is not just the amount of light that changes, but also its colour.

We found that cells in the mouse SCN were able to detect these changes in colour via a mechanism analogous to conventional colour vision (Walmsley et al, PLoS Biology 2015).

DOI: https://doi.org/10.1371/journal.pbio.1002127

We were subsequently able to show that changes in colour resembling twilight were specifically associated with reduced circadian responses to light, and that this mechanism buffers the circadian system against day-day variations in cloud cover, a fundamental sensory control mechanism that ensures robust circadian timing in the natural world (Mouland et al, Current Biology 2019).

DOI: https://doi.org/10.1016/j.cub.2019.10.028

Pathways for clock-controlled physiology

Cells that express VIP are critical for the normal functioning of the SCN but their roles in relaying time of day information from the clock have long-remained uncertain. We showed that, in fact, these clock VIP cells provide precisely timed signals that constitutes a key route by which the circadian system coordinates rhythms in hormone secretion, cardiovascular function and behaviour (Paul et al, Nature communications 2020).

DOI: https://doi.org/10.1038/s41467-020-15277-x

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