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:
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Does SCN firing induce or shift circadian gene expression and firing in (subsets of) target neurons?
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Do these neurons encode daily timing signals from different SCN neuron types?
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How do these neurons integrate circadian input with signals from other brain regions?
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And, ultimately, how do rhythms in these neurons regulate circadian outputs?
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.
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.
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.
Approaches
Circadian behavioral analysis
(wheel running, infrared tracking, feeding)
In vitro imaging
(time-lapse recording of calcium and clock genes)
Manipulation and measurement of hormones
(ELISA, drug delivery)
Neuromodulation
(in vivo, in vitro optogenetics, chemogenetics)
Neurogenetics
(CRISPR/Cas9 editing of clock genes and receptors)
Complex behavioral analysis
(video tracking, machine learning)
In vivo imaging
(fiber photometry recording of calcium and clock genes)
Neuroanatomy
(circuit tracing, IHC, confocal imaging)
Open-source tool development
(3D printing, laser cutting, electronics)
