Biological Clocks Orchestrate Behavioral Rhythms by Sending Signals Downstream

Different groups of neurons program biological clocks to orchestrate our behaviors by sending messages in a unidirectional manner downstream, a team of biologists has found.

The study, which appears in the journal Nature Neuroscience, focused on clock neurons in the fruit fly Drosophila and sought to understand the larger role of biological clocks—also known as circadian rhythms.

“We’ve known for a long time how clock neurons keep time, but we haven’t understood how rhythms in a fairly small number of clock neurons control the behavior of an entire animal,” explains Justin Blau, the paper’s senior author and a professor in NYU’s Department of Biology and at NYU Abu Dhabi. “Our findings reveal a ‘circadian circuit’ in which signals go from one set of neurons to another in a unidirectional manner, and this circuit connects clock neurons to the central brain areas that regulate activity and sleep.”

Image shows a waterfall.
Different groups of neurons program biological clocks to orchestrate our behaviors by sending messages in a unidirectional manner downstream, a team of NYU biologists has found. Image adapted from the NYU press release.

In their studies, the scientists found that the fly’s clock neurons send signals to Leucokinin, or LK, neurons, which in turn send signals to Leucokinin Receptor, or LK-R, neurons.

Clock neurons have their own molecular clocks that allow them to signal at specific times of day. But how is this time information transmitted through the brain? Blau and his team found that the rhythmic signaling of clock neurons drives rhythms when the downstream LK and LK-R neurons signal—even though LK and LK-R neurons do not have molecular clocks themselves.

The researchers also found rhythms in the signaling of DH44-expressing neurons—another set of neurons previously shown to be downstream of clock neurons. So, the researchers concluded, transferring rhythms from clock neurons downstream seems to be a general mechanism for how time flows through the brain.

About this neuroscience research

The study’s other authors included Matthieu Cavey, Ben Collins, and Claire Bertet—NYU postdoctoral fellows at the time of the study.

Funding: The research was supported by grants from the National Center for Research Resources, part of the National Institutes of Health (C06 RR-15518-01), the European Molecular Biology Organization, the Charles H. Revson Foundation, the Human Frontier Science Program, the NYU Abu Dhabi Research Institute, and the National Institutes of Health (EY017916, GM063911).

Source: James Devitt – NYU
Image Source: The image is adapted from the NYU press release.
Original Research: Abstract for “Circadian rhythms in neuronal activity propagate through output circuits” by Matthieu Cavey, Ben Collins, Claire Bertet and Justin Blau in Nature Neuroscience. Published online February 29 2016 doi:10.1038/nn.4263


Abstract

Circadian rhythms in neuronal activity propagate through output circuits

Twenty-four hour rhythms in behavior are organized by a network of circadian pacemaker neurons. Rhythmic activity in this network is generated by intrinsic rhythms in clock neuron physiology and communication between clock neurons. However, it is poorly understood how the activity of a small number of pacemaker neurons is translated into rhythmic behavior of the whole animal. To understand this, we screened for signals that could identify circadian output circuits in Drosophila melanogaster. We found that leucokinin neuropeptide (LK) and its receptor (LK-R) were required for normal behavioral rhythms. This LK/LK-R circuit connects pacemaker neurons to brain areas that regulate locomotor activity and sleep. Our experiments revealed that pacemaker neurons impose rhythmic activity and excitability on LK- and LK-R-expressing neurons. We also found pacemaker neuron–dependent activity rhythms in a second circadian output pathway controlled by DH44 neuropeptide–expressing neurons. We conclude that rhythmic clock neuron activity propagates to multiple downstream circuits to orchestrate behavioral rhythms.

“Circadian rhythms in neuronal activity propagate through output circuits” by Matthieu Cavey, Ben Collins, Claire Bertet and Justin Blau in Nature Neuroscience. Published online February 29 2016 doi:10.1038/nn.4263

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