Besides the well known human senses (sight, hearing, smell, touch, taste, position) , scientists have recently discovered the 7-th sense, I will name hereinafter, temporal sense.

The temporal sense is linked to the circadian rhythms and helps the brain managing the time-related mechanisms of the body.

Computer users know that it incorporates a clock device, at a fixed clock frequency. Human beings have this mechanism although they are not computers. The brain clock device works at variable frequencies (between 20 to 180 Hz), that are strong related to the emotional states we experience in that moment.

Who hadn't waited from for someone who didn't appear ? Have you felt like time passes slower ? Or when you found yourself into a car stuck in a traffic jam and you have to arrive to an important meeting, haven't you felt time passing faster ?

In most of these situations, and also in the temporal orientation of the body in the environment in which we live, are taken care of by the suprachiasmatic nuclei (SCN), located in the anterior area of the hypothalamus.

For a better understanding I suggest you a short presentation of the anatomy of the hypothalamus. Hypothalamus forms the basal part of diencephalons represented by infundibulotuberian region. It is divided into three main regions, each with nuclei that are differentiated based on both structure and function. The suprachiasmatic region is located in the anterior (rostral) hypothalamus just dorsal to the optic chiasm. Located in this region are the supraoptic, paraventricular, suprachiasmatic, and the anterior nuclei. The tuberal region is located in the middle hypothalamus and includes the ventromedial, dorsomedial, and the infundibular nuclei. The mammilary region is located in the posterior (caudal) hypothalamus and includes the mammilary bodies and the posterior nuclei. Most nuclei of hypothalamus are reciprocally connected to a number of regions of the Limbic System including the amygdala, hippocampus, and the septal area 1. The suprachiasmatic nuclei, which receive a projection from the retina and the geniculate nuclei of the thalamus, maintain the biological clock by controlling the circadian (daily) cycle of sleep-wakefulness.

Discovered in 1877, eye pigments known as opsins, which are linked to vitamin A and located in the retina, enable mammals to see by absorbing light and transferring visual signals through the optic nerve to the brain. The scientists discovered two new molecules called cryptochromes, CRY1 and CRY2, which are linked to vitamin B2 and located in a different part of the retina. Cryptochromes enable animals and humans to synchronize they circadian clock by absorbing blue light and transferring the light signal through the optic nerve to a different part of the brain from the center for vision.

Severing the optic nerve abolishes both vision and circadian photo-response, as scientists claim. However, because pigments for vision and circadian clock occur in different parts of the retina, some blind people who have lost the part of the retina containing opsins still retain cryptochrome region, maintain circadian rhythm.

Scientists also discovered that the circadian clock is controled by a genetic mechanism. Analysing the circadian patterns of activity in mutant fruit flies (Drosophila Melanogaster) they identified several genes that encode essential elements of the clock. Note1 . Mutations of these genes can either speed up or slow down the clock, giving flies with days of 20 or 28 hours. Alternatively, mutations can destroy althogether the ability of a fly to be rhythmic.

Short description of clock molecules in Drosophila Melanogaster.

In the fly, rhythm is set by the action of two proteins, PER and TIM, made by the period (per) and timeless (tim) genes, respectively. All cells of the fly have per and tim genes, but the brain cells set the body clock. PER and TIM proteins accumulate in the nuclei of eye cells sensitive to light, as well as in pacemaker cells of the central brain.

The fly circadian rhythm begins around noon when the expression of the clock genes period (per) and timeless (tim) is stimulated by the transcription factors BMAL and CLOCK. Note2. Per and tim genes transcribes their DNA into mRNA (m - from messenger), molecules essential to create the PER and TIM proteins, but only after sunset does the accumulated RNA prompts the cell to stockpile the PER and TIM proteins. Note3. Initially the proteins are rapidly degraded whithin the cytoplasm, especially PER. However, the PER has a specialised binding site, which enables it to associate with TIM as heterodimers. These dimers are much more resistant to degradation, and in the act of association, surfaces of the protein that hold PER in the cytoplasm are obscured and the dimers become able to enter the nucleus. This is a key event because these clock proteins have another property - they can control the activity of various genes. Per and tim genes expresion is suppressed by their own dimerised protein product, closing the feedback loop. Near dawn, the PER/TIM heterodimers disintegrate (Note4) and the genes are released from inhibition to become active again and reinitiate the cycle. Because of the long lags between gene activation and turn off, the whole sequence takes about 24 hours and is self-sustaining.

The findings also suggests how light exposure at the different times of day adapts the clock, such as adjusting to a new time zone. For example, Young et al. found in 1996, that flies exposed to one hour of daylight in the evening, around 10 PM, delayed the normal night time accumulation of the TIM protein, and setted the clock back by four to five hours. In contrast, flies exposed to daylight an hour before dawn setted the clock ahead by one to two hours. On the other hand, constant light disturbs the biological clock and suppresses circadian rhythms in a variety of organisms including mammals, as author Young notes.

Studies in mammals have advanced our understanding of the clock mechanism. The human equivalents of the Drosophila per and tim gene have been identified. The parallels between Drosophila Melanogaster and mammalian forms of the genes show that evolution has conserved not only the property of circadian timing but also its molecular basis, indicating how deeply the clock is entrenched in our make up. Scientists also discovered the human equivalents of CLOCK and BMA proteins.

In addition, our habits may affect the clock independentely of light because recent studies has shown that applied schedules of physical activity can alter circadian period. Although the behaviour of clock molecules in the SCN is not known. Nevertheless, these findings have important therapeutic considerations in situations where the clock is desynchronised - for example, in jet lag, shift work, and particular forms of depresion.

Conclusions :

I. Humans and mammals have a temporal sense that evolution conserved from the simpliest organisms like Drosophila.
II. Most of time-related mechanisms of our body are related to SCN and circadian rhythms.

References :
1. Parent, A. (1996). Carpenter's human neuroanatomy (9 th ed.) London : Williams & Wilkins.
2. Ibata et al. (1999). Functional morphology of the suprachiasmatic nucleus. Frontiers of Neuroendocrinology, 20(3), 241 - 268.
3. Wittkovski et al. (1999). Cell and molecular biology of the pars tuberalis of the pituitary. International Review of Cytology, 185, 157 - 194.
4. Web article - Discovery : Experiments confirm novel eye pigment controls circadian rhythm.
5. Web article - bmj.com Hastings 317 (70174) : 1704 - 1707.
6. Web article - Light sets the molecular controls of circadian rhythm.

Notes :
Note1 - In normal fruit flies, the geneticaly encoded day is equal to 24 hours.
Note2 - Transcription factors include a protein, and the existence of ATP, GTP, UTP, CTP + RNA polimerase DNA dependent + Mg2+ or Zn2+ ions.
Note3 - The per and tim are active in the early part of the night and proteins start to accumulate later in the night.
Note4 - Under influence of cryptochrome (which conformation is allostericaly changed by absorbed blue light) that binds to the TIM portion of PER/TIM heterodimers and removes it from heterodimer, promoting that way the fast disintegration.