Schematic of input to, molecular and electrical rhythms of, and outputs from the SCN

Organisms have evolved endogenous  circadian  (~24 h) rhythms to anticipate reliable daily events such as the light cycle. These rhythms are synchronized to local time by the master circadian pacemaker, the suprachiasmatic nucleus (SCN). The SCN, with its well-defined inputs (light) and reliable outputs (daily rhythms) is a uniquely advantageous model in which to investigate the fundamental neuroscience question of how genes, neurons, and circuits interact to influence behavior and physiology.

Dissecting the circuits that regulate circadian rhythms is also crucial to understand how their disruption contributes to disease including metabolic, cardiovascular, and mood disorders. Determining the coding strategies of these circuits will inform experiments investigating the circuit basis of circadian dysfunction that both leads to, and is a symptom of, disease.

The overarching research goal of the Jones Lab is to understand how circadian output from the SCN is encoded by downstream neurons to ultimately generate diverse endocrine, autonomic, and behavioral rhythms with different phases and waveforms. We aim to answer critical questions including:

  • Does SCN firing induce or shift circadian gene expression and firing in (subsets of) target neurons?

  • Do these neurons encode daily timing signals from different SCN neuron types?

  • How do these neurons integrate circadian input with signals from other brain regions?

  • And, ultimately, how do rhythms in these neurons regulate circadian outputs?

Calcium trace from the SCN
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Current Projects

What are the transfer functions for circadian outputs?
We don't mechanistically know how SCN rhythms are encoded by target neurons to generate outputs that each peak at different times of day. To address this, we are investigating how target neurons encode rhythmic SCN input by defining the "transfer function" that takes place in target neurons and determining the role of local clocks in this encoding process.
Diagram showing transfer function for circadian outputs
Diagram showing how hormone can change circadian outputs
How do hormones and sex influence circadian circuits?
Are differences in circulating hormones and sex both necessary and sufficient to generate circadian outputs? Hormone differences in circadian rhythms have been implicated in disease but are largely understudied. Our lab is investigating how rhythms in the brain reflect hormone differences in circadian outputs and how brain clocks are regulated by hormone release.
Diagram showing how the circadian system can compensate for noise
How does the circadian system overcome noise?
How do circadian circuits distinguish between daily input from the SCN and "noise" - non-circadian signals that can influence rhythmic activity? How can a noisy rhythm provide a reliable timing cue to the rest of the brain and body? We are investigating how the circadian system integrates SCN input and noise, and if particular input neurons are more robust to noise than others.
Calcium trace from the SCN
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Approaches

Circadian behavioral analysis
(wheel running, infrared tracking, feeding)
Locomotor activity and feeding rhythms over several days in a light cycle and in constant darkness
Fluorescent reporter of SCN activity and bioluminescent reporter of the SCN molecular clock
In vitro imaging
(time-lapse recording of calcium and clock genes)
Manipulation and measurement of hormones
(ELISA, drug delivery)
Corticosterone rhythms in wild-type, clock knockout, and estrogen supplemented mice
Neuromodulation
(in vivoin vitro optogenetics, chemogenetics)
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Neurogenetics
(CRISPR/Cas9 editing of clock genes and receptors)
CRISPR/Cas9 can selectively delete the core clock gene BMAL1 from specific PVN neurons
Complex behavioral analysis
(video tracking, machine learning)
Automatically-scored behavioral rhythms in wild-type and circadian mutant mice
In vivo imaging
(fiber photometry recording of calcium and clock genes)
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Neuroanatomy
(circuit tracing, IHC, confocal imaging)
Viral tract tracing to and from the SCN and PVN
Open-source tool development
(3D printing, laser cutting, electronics)
A picture of an automated hormone collector, a wireless IR tracker, and an automated feeder
Calcium trace from the SCN
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