Neurology Central

#NCintroduces… Mammalian chronobiology and circadian rhythms

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Welcome to the first edition of our new column, #NCintroduces, which aims to give students, early career researchers and those interested in the field an introduction to an exciting area or idea in neuroscience. In this installment, Tom Naughton, a UCL  (London, UK) Biomedical Sciences graduate and now-lab technician at  the UCL Cancer Institute, introduces the complex world of circadian rhythms.

How a genetic feedback loop tunes biology

As the Earth basks in the light of the sun, its rotation produces a 24-hour cycle of daylight and darkness. Much of life on Earth has adapted to this relentless rhythm. Single-celled and complex multicellular organisms synchronize their behavior with the daily solar cycles, causing both behavioral and molecular processes to lock into phase with a natural rhythm. Whilst biological patterns may differ from species to species, the rule is usually the same: they oscillate with a period of close to 24 hours, otherwise known as a circadian rhythm. [1]

I say “close to”, because the oscillation rarely matches a day exactly. It is often slightly longer, or slightly shorter than the day’s length. The existence of an external stimulus (known as a zeitgeber, or entrainment signal), like the steady rhythm of daylight, resets the internal clock every day. In fact, the activity patterns of organisms tend to drift, or ‘free-run’, without this input, becoming progressively earlier or later each day, according to the period of the internal cycle. As soon as the light/dark cycle returns, they snap back into the correct rhythm, resulting in a ‘phase-shift’. [2]

“Therefore the entrainment signal is not the cause of the rhythmicity of the organism, as the rhythm still exists in its absence…”

Therefore the entrainment signal is not the cause of the rhythmicity of the organism, as the rhythm still exists in its absence. Instead, circadian cycles are intrinsic, and can be influenced by an external signal. The most prevalent and powerful entrainment signal is daylight, but it is not the only one. For example, strict feeding regimes have also been shown to maintain the rhythmicity of internal clocks. [3]

The study of biological rhythms has been awarded its own title: chronobiology. From chronobiological investigations, we have learned that animal behavior is governed by an oscillator, which cycles with a circadian rhythm and can respond to one or more external stimuli.

In the multitude of different organisms that exist on Earth, many different oscillators have evolved. Model organisms, whose clock systems have been studied in detail, range from fruit flies to bacteria. In mammals, which this article focuses on, an area of the brain known as the suprachiasmatic nucleus of the hypothalamus (SCN), located just above the region where the two optic nerves intersect, is thought to be the home of this oscillator.

The mammalian oscillator in action

The mammalian SCN is made up of a mixed population of neurons [4], which are intrinsically rhythmic. In other words, they show impulse patterns that oscillate with a circadian rhythm. [5] Destroying the SCN tissue in a live animal disrupts rhythmic behavior, and by transplanting SCN tissue from healthy donor animals into those afflicted, it is possible to restore it. [6]

“Even when SCN neurons are dissociated from their host and kept alive in a dish, this basic rhythmicity remains…”

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