Novel molecular clues behind nocturnal behavior

Research provides new insights into sleep/awake circadian rhythm patterns

Date: August 22, 2016

Source: University of California - Irvine

Research from University of California, Irvine scientists and their colleagues offers new insights into why many animals sleep at night and are active during the day, while others do the reverse.

A team headed by Qun-Yong Zhou, UCI professor of pharmacology, examined the day/night patterns of monkeys (diurnal) and mice (nocturnal) and found that although both process light through the eyes in a similar way, the signals that determine sleep/awake modes are sent to the brain via different routes and produce completely opposite sleep/awake patterns.

"Since humans are diurnal, this has clear implications for potential novel treatment of certain sleep or mood disorders," said Zhou, the study's lead author. Results appear online in Molecular Brain.

Sleep/awake patterns are among the basic physiological functions in virtually all organisms that are governed by circadian rhythms. These fundamental time-tracking systems anticipate environmental changes and adapt to the appropriate time of day.

Zhou and his colleagues discovered that the sleep/awake switch exists in the eyes within the intrinsically photosensitive retinal ganglion cells, or ipRGC. Previously, a brain region called the suprachiasmatic nucleus, or SCN, was believed to house the master clock that keeps the body on an approximately 24-hour schedule.

The current findings give the eyes a more central role in the control of the sleep/awake cycle. In the nocturnal mice, ipRGC and SCN appear to function similarly, and either could serve as the timekeeper. But in the diurnal monkeys, the eyes' ipRGC seems to be dominant.

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Blind Cavefish Froze Its Internal Clock to Save Energy

By Elizabeth Palermo, Staff Writer | September 24, 2014 02:13pm ET

Some creatures will go to great lengths just to save a little energy. Take the blind Mexican cavefish; this super-efficient animal uses almost 30 percent less energy to survive than its counterparts in surface waters, and it accomplishes this in a rather interesting way, a new study suggests.

The blind Mexican tetra or cavefish (Astyanax mexicanus) saves energy by forgoing circadian rhythms, according to researchers at Lund University in Sweden. Sometimes referred to as an internal clock, circadian rhythms help many organisms — including animals, plants, fungi and even certain bacteria — coordinate their behavior and physiology with the day-night cycle, according to study researcher Damian Moran, a postdoctoral student in the Lund University department of biology.

This clock provides one of its most important functions by controlling metabolism, or the chemical reactions involved in maintaining healthy cells and breaking down molecules to gain energy. Circadian rhythm helps ensure these reactions occur in advance of when an organism will most need energy, Moran told Live Science.

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Siberian Hamsters Show What Helps Make Seasonal Clocks Tick

Sep. 23, 2013 — Many animals, including humans, have internal clocks and calendars to help them regulate behavior, physiological functions and biological processes. Although scientists have extensively studied the timekeeping mechanisms that inform daily functions (circadian rhythms), they know very little about the timekeeping mechanisms that inform seasonal functions.

New research to be published this week in the online early edition of the Proceedings of the National Academy of Sciences shows, for the first time, that this measurement of seasonal time has an epigenetic component. Epigenetics refers to an alteration in gene expression that occurs without a change in the sequence of DNA molecules.

The research used Siberian hamsters, which only breed in the late spring and early summer, when days are the longest. It revealed the molecular mechanism behind how these hamsters avoid breeding in the fall and winter, thereby preventing births during the cold, resource-scarce winter months.

Here's how the mechanism works: Exposure to short periods of daylight decreases DNA methylation in the hamsters' hypothalamus. (With DNA methylation, a methyl group -- one carbon atom and three hydrogen atoms -- attaches to a gene, thereby altering its expression.) In turn, the decreased DNA methylation stimulates the expression of a gene that shuts down the hamster's reproductive competency.

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Fruit Flies Reveal New Evolutionary Link for Studying Human Health: How They Control Body Temperature Through Circadian Rhythm

ScienceDaily (Sep. 13, 2012) — New research reveals that fruit flies and mammals may share a surprising evolutionary link in how they control body temperature through circadian rhythm, unlocking new ways to study the insects as models of human development and disease.

The study posted online Sept. 13 by Current Biology reports that similar to people, Drosophila fruit flies -- a common research tool in life sciences -- have a genetically driven internal clock. This circadian clock prompts the insects to seek out warmer or cooler external temperatures according to the time of the day. Cold-blooded creatures change behavior to alter body temperature, usually by seeking out different external temperatures. But fruit flies are the first cold-blooded species to demonstrate their modification of temperature preference behavior is controlled by a circadian clock.

Continued:  http://www.sciencedaily.com/releases/2012/09/120913123223.htm

Blind Cave Fish Can Tell Time

A blind cave fish that has spent millions of years underground isolated from evidence of day and night still has a working biological clock, albeit an unusually distorted one, scientists find.
This research could yield new clues on how such clocks might work in animals in general, researchers added.

Internal clocks known as circadian rhythms help animals, plants and other life to adapt their daily activities to the cycle of day and night. These clocks do not always follow a precise 24-hour schedule,
so to keep synchronized with the natural world, they get reset on a daily basis by signals such as daylight.

One question circadian clocks bring to mind is whether and how those creatures that live in perpetual darkness still keep time. For instance, about 50 fish species worldwide have evolved to live without
sunlight in caves, many times losing their eyes.

"Cave fish give us a unique opportunity to understand how profoundly sunlight has influenced our evolution," said researcher Cristiano Bertolucci, a chronobiologist at the University of Ferrara in Italy.

Bertolucci and his colleagues investigated a Somalian cave fish (Phreatichthys andruzzii), which has lived isolated for 1.4 million to 2.6 million years beneath the desert. They compared swimming behavior and clock-gene activity seen in a relatively normal fish, the zebra fish (Danio rerio), with that seen in the cavefish.

Zebra fish had circadian clocks that were very rhythmic, synchronizing with cycles of darkness and light. Unsurprisingly, the blind cave fish's behavior did not similarly keep in sync with the light.
However, when a different rhythmic signal was used — a regular time at which the fish were given food— the circadian clocks of both zebra fish and cave fish matched it. This revealed that cave fish clocks could work if given a relevant signal such as food.

A closer look at the clock genes of the subterranean fish revealed mutations in two major light-sensitive chemicals known as opsins that rendered them unable to respond to light and thus kick-start circadian rhythms. Oddly, when the cave fish were given a chemical known to activate clock genes in normal fish, the blind fish's circadian rhythms moved at a bizarrely long cycle of up to about 47 hours long.
The fact that cave fish clocks no longer follow a 24-hour cycle suggests "maybe these animals are in the process of losing their clocks," researcher Nicholas Foulkes, a chronobiologist at the Karlsruhe Institute of Technology in Eggenstein, Germany, told LiveScience.
These complex mechanisms appear hard to alter, however, given how they often seem largely unchanged across many different species, "and therefore it might take a lot of time to actually lose them. As part of this ongoing process, this could be why this clock is broken, running at 47 hours long instead of 24 hours long. Maybe in a million years, this fish might not have a clock at all," Foulkes added. It remains uncertain whether the clock still serves them any purpose whatsoever.

Much is poorly understood when it comes to how light regulates circadian rhythms. Analyzing how these clock genes work in blind cave fish has thus provided "the first clues" in solving the mystery as to what light-sensitive molecules are key in other fish, Foulkes said.

"This study sets the stage for a more complete understanding of how clocks respond to their environment," Foulkes added.

The scientists detailed their findings online on Sept. 6 in the journal PLoS Biology.
http://www.livescience.com/15923-blind-cave-fish-circadian-rhythms.