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Genetics of time perception


Time is the fundamental dimension for animal’s survival. The animal brain is the result of evolution to orchestrate temporal information across a wide spectrum of time scales. For example, it takes several minutes for an animal to be satiated. Also, satiated states are maintained for several minutes to hours. This feature indicates that generic satiety circuits need to compute ‘interval timing’ information for inducing and keeping satiety.


Interval timing refers to the discrimination of durations in the seconds-to-minutes ranges. Interval timing is a pivotal function of the human brain to support our cognitive ability such as memory, attention, and decision-making61–63 (Fig. 12).

We have established three independent interval timing model in fruit fly.


First, we previously identified two novel behavioural paradigms of male Drosophila that fits the current ‘internal clock model’ of interval timing. Internal clock model (pacemaker-accumulator model, PAM) constitutes of a pacemaker, mode switch, accumulator, memory circuit, and a comparator circuit (Fig. 13A). We already identified all of PAM components exist in neural circuits regulating rival-induced prolonged mating behaviour. In this interval timing paradigm, clock genes period/timeless play crucial role as a pacemaker and neuropeptides PDF/NPF signaling function as an accumulator (Fig. 13B). Clock genes regulate interval timing although the precise molecular mechanisms are not well investigated.



Second, we recently identified that circadian clock genes are specifically associated with sexual satiety circuit. We found that Drosophila males exhibit a shortened mating duration for guarding female when sexually satiated, called ‘Shorter-Mating-Duration (SMD)’. Interestingly, sexual satiety depends on the circadian clock genes clock/cycle, but not timeless/period.

Third, many studies indicate that clock genes are involved with feeding behaviour of animals. In mammals, the central suprachiasmatic nucleus (SCN) of the hypothalamus function as a master pacemaker to d


rive rhythms in activity and rest, feeding, body temperature, and hormones. As described above, hypothalamus is a centre of satiety control as well as function as integration centre of central and peripheral clock. Many studies suggest that clock genes are integrated into metabolism and energetics and it is well known that satiety is closely related to homeostatic mechanisms of body control to maintain the appropriate metabolic states. In Drosophila, many studies indicate that clock genes play a central role to regulate feeding and metabolism. Thus, the study of satiety control can answer the question how the same clock genes regulate the different scale of timing behaviours (circadian rhythm/interval timing) in a circuit-dependent manner.


Finally, we recently found that temperature affect the time perception of male flies. We are now screening various mutants to find the sensory circuits connecting it to central PAM circuit.


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