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Transforming the understanding
and treatment of mental illnesses.

Alison Bashford, Winner of the 2021 NIMH Three-Minute Talks Competition

Watch on YouTube.


Alison Bashford: One thing we know about circadian rhythms is that light from our environment enters the retina and through retinal projections, to our brain’s central circadian pacemaker, it influences different physiological rhythms. And while we have a really good understanding of how retinal cells send light information to the central pacemaker, it is not yet known how non-photic cues are communicated to the pacemaker resulting in additional adaptations to our daily rhythms. 

One particular non-photic cue that is of interest is stress, because we do know that stress affects the pacemaker, leading to changes in things like hormone release and sleep pattern changes that ultimately affect our mental and physical health.

So this central circadian pacemaker is called the suprachiasmatic nucleus of the hypothalamus, or the SCN, and one likely candidate for the relaying of this stress information to the SCN is the PVT, or the paraventricular nucleus of the thalamus, because it both sends robust projections to the SCN and is activated in response to foot shock stress.

The question then becomes, does the PVT relay stress information to the SCN to tune circadian activity? So firstly, after we've removed light as a daily environmental cue and allowed animals to adapt to 24 hours of darkness, we foot shock these animals two hours after they normally wake up. And what we'd expect to see, given the circadian activity of mice in total darkness, is that the onset of their activity is earlier and earlier each day. And while we did see this in control mice, in animals who were shocked, their onset activity was later than expected, indicating that these foot shocks cause a phase shift or a delay in the onset of circadian activity.

Next, we did bulk fiber photometry calcium imaging to record population activity from only those PVT cells that project to the SCN. We saw that they were activated in response to foot shock.

And so this data has really led us to consider that these PVT to SCN projections are communicating information about stress to the circadian system. And what we would want to do next to confirm this possibility is to pair foot shocks with the specific chemogenetic inhibition of these PVT to SCN projections. And if they are necessary for this information relay, their inhibition during foot shock should prevent a phase shift seen in circadian activity.

Ultimately, this work will provide insight into how non-photic cues affect circadian output and therefore mental and physical health.