Florian Storch, McGill University
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At the heart of the brain is a neurological clock, called the suprachiasmatic nucleus, which ticks “genetically” to keep a roughly 24 hour schedule. The signal from this “master clock” is relayed around the body where it helps to set the metabolic tone throughout the day. Disturb the clock and you suffer from jetlag; disable the clock and scientists had thought that animals would lost track of time. But if you look carefully enough another rhythm – indicating the existence of a second body clock – this one running with a 4 hour rather than 24 hour rhythm – appears. Florian Storch explained to Chris Smith...
Florian - When you eliminate the circadic clock for mice and study them in constant darkness where they are not exposed to any timing cue, these mice will not show complete arrhythmia but often times still show some rhythmicity which indicates there is another timer which drives rhythm in the range of 2 to 6 hours.
Chris - So, if it isn’t the suprachiasmatic nucleus, the master clock in the brain, which is driving this 4-hour cycle; what is?
Florian - Yeah. So, when we looked at these animals under constant condition, constant darkness which are just like in the circadian clock, and we observe these 4-hour rhythms. We were thinking this rhythmicity locomotor activity can also be considered as a rhythmicity and arousal. So, when the animal jumps into the running wheel, the animal is aroused. And there is quite some literature about arousal regulation and what has been prominently associated with arousal promotion is dopamine because mice which lack dopamine are actually very lethargic and this is very different from the other monoamines. And so we were thinking maybe dopamine might play a role in these 4-hour activity cycles.
Chris - And how would you know that the dopamine was driving the activity, and that the escalation in dopamine wasn’t just a consequence of the act of the activity?
Florian - When we draw our attention to mice which were lacking the dopamine transporter, and the mice will show elevated dopamine tone and show great length in the activity cycle at 12 hours about. This kind of pointed to us that the dopamine somehow is dictating the period of this oscillation.
Chirs - Why would the brain need this? What purpose could it possibly serve?
Florian - There’s evidence that it actually can provide a kind of selective advantage. This has been demonstrated in the common vole which shows 3 to 4 hour oscillations in its foraging behaviour. And this is very synchronous amongst the vole population. And it’s believed because they are in the synchronous fashion, coming out of the burrows and exposing them self to a predator, that it actually reduces predatory risk. So, we think that really this other oscillator which we now describe in this publication is really conferring social synchrony and it might be the reason why we have, for instance, three meals a day and not five, not one, might be due to the function of this oscillator. So, generally it confers social alignment and social synchrony which is, especially with species which are social species, might be a real selective advantage.
Chris - Now moving from an animal and being a bit speculative for a minute. There are a number of human conditions which are associated with an elevation in dopamine tone in the brain – schizophrenia and some of the psychotic illnesses is one example. Bipolar disorder overlaps with that. Do you see any association in what happens to humans afflicted by these conditions and what you found in your experimental animals?
Florian - We were really struck when we looked at sleep-wake recordings from bipolar and schizophrenic patients, how similar in some cases the sleep-wake abnormalities are to our animal models. So, there are some bipolar patients which suffer from rapid cycling. They observe a manic episode every 48 hours. And we have animals which have been treated long-term with methamphetamine which also increase this dopamine tone; and these animals will show 48-hour cycling suggesting that in bipolar and also in schizophrenics, the sleep-wake cycle operation associated with these illnesses may be based on dysregulation of this oscillator we describe here.