NYU biologists find new function for pacemaker neurons

A study by New York University researchers reveals a new function for the nerve cells that regulate circadian rhythms of behavior in fruit flies.

The nerve cells, called pacemaker neurons, contain a molecular clock that controls a 24-hour circadian rhythm in activity similar to the rhythms in sleep/wake cycles found in humans and many other organisms. It was previously known that pacemaker neurons receive visual signals to reset their molecular clocks, but scientists did not have any evidence that they transmitted information to their target cells, as most other neurons do.

The current study shows that pacemaker neurons do in fact transmit signals and are required for a rapid behavior, according to the paper, published in the January 20th issue of Neuron. The study was conducted by Esteban O. Mazzoni, a graduate student in NYU’s Biology Department, Biology Professor Claude Desplan, and Assistant Biology Professor Justin Blau. The finding suggests it may be possible to identify genes that can be used to treat problems such as sleep disorders and jet lag.

The researchers examined the role that pacemaker neurons play in helping Drosophila larvae avoid light. Drosophila is a species of fruit fly commonly used in biological research. Fruit fly larvae foraging for food avoid light, presumably to keep away from predators. Unlike adult Drosophila, the larvae only have one structure for gathering visual cues, called Bolwig’s Organ. This organ senses the amount of light in the environment and transmits that information to the pacemaker neurons to reset their molecular clocks.

In the experiments described by Mazzoni, Desplan, and Blau, fly larvae were placed in the center of a Petri dish with one side dark and the other illuminated. Normal larvae exhibited the natural behavior and clustered on the dark side. However, when the larvae had their pacemaker neurons disabled, they were as blind as larvae that had their light-sensing organs removed and distributed themselves evenly between the light and dark halves of the Petri dish.

Further experiments showed that, in addition to transmitting the light information, the pacemaker neurons also modulate the sensitivity of larvae to light, generating a circadian rhythm in visual sensitivity. The experiments revealed that fruit fly larvae are most sensitive to light at dawn and least sensitive toward dusk.

The study demonstrates that pacemaker neurons are doing much more than scientists had suspected. They not only relay visual signals to target cells, but are also act as filters, using their molecular clocks to adjust the intensity of the transmitted signal depending on the time of day.

Almost all of the genes that make up Drosophila’s molecular clock have counterparts with similar functions in mammals. Because of this similarity, it may be possible to identify genes in fruit flies that can be used to treat problems in people, such as sleep disorders and jet lag.