Biological Clock
The Biological Clock is an endogenous mechanism responsible for regulating various physiological and behavioural rhythms in mammals. Mammals are warm-blooded vertebrates that belong to the class of the Mammalia. They can be characterized as eukaryotes observed through their endocrine and phenological features. Also, mammals give birth to live young, who are then fed milk produced by the maternal mammary glands. This class includes species like primates, carnivores, rodents and ungulates. Rhythmic changes occurring due to the biological clock happen in all mammals. These changes are genetically programmed and can be observed yearly, monthly and daily. Daily cyclical rhythms are also called Circadian Rhythms (from the Latin circa dies, “about a day”). Period lengths less than 24 hours are called ultradian. (Biological Clock)
Process
The regulators responsible for the generation and synchronization of these circadianrhythms reside in the supra-chiasmatic nucleus (SCN) of the anterior of theHypothalamus. It is organized in a hierarchy of oscillators.
Hypothalamus
Hypothalamus is the highest cerebral integrator of the autonomic functions. Itcoordinates neural and hormonal regulative activity. The morphologicalcharacteristics of the hypothalamus are as follows; it is divided into two areas, theMagnocellular area and Parvocellular area that consist of large and small cells andreach the posterior and anterior lobes of the pituitary gland respectively, thus,releasing their hormones.
The SCN is responsible for coordinating independent peripheral oscillators so that acoherent rhythm is synchronized at the organismal level. The Clock mechanism consists ofa network of transcriptional – translational feedback loops that have a continuous cyclic 24hours expression pattern of core clock components. These are expressed as genes whoseprotein products are necessary for the generation and regulation of circadian rhythmswithin individual cells throughout the organism (Takahashi J.S & Ko C.H, 2006).
The positive elements of the primary feedback loop are the CLOCK and BMAL1. These belong to the transcription – factor family, (basic helix-loop helix) bHLH -Pas(Period-Arnt-Single-minded). The CLOCK and BMAL1 heterodimerize and initiatetranscription of specific target genes. The negative feedback, however, is achieved by thetranslocation of these heterodimers back to the nucleus, thus suppressing their owntranscription. In other regulatory loops, CLOCK:BMAL1 heterodimers activate transcriptionof retinoic acid (Takahashi J.S & Ko C.H, 2006).
The autoregulatory feedback loops are controlled by post – translational modifications,such as phosphorylation and ubiquitination. These processes affect the stability andnuclear translocation of the core clock proteins. Casein kinase 1 epsilon and casein kinase1 delta are critical factors that regulate the core circadian protein turnover in mammals.
Regulation of Biological clock
Light is the most important stimulus for resetting the biological clock. The Light-Dark cyclemirrors the intensive changes in the environment like the alterations in temperature,availability of food and predation. (Halle S. & Stenseth N.C., 2000)Animals are divided into two major groups. The first group consists of the diurnal animals,which can be more active and carry out their daily routine during the day time, whereasthe second group comprises of nocturnal animals which are primarily active at night.However, both groups have in common the hormone rhythm of Melatonin release fromthe pineal gland. Its role is the transduction of light/dark information into hormonalsecretions in a rhythmic pattern. Secretion of melatonin depends on light exposure.Decreased illumination (darkness) acts positively while strong illumination (daylight) actsnegatively on melatonin production. Melatonin in certain species influencesreproduction, torpor and changes in pelage (Bartness T.J. et al, 1989).
Glutamate (Glu) is the neurotransmitter that mediates light stimulation. Together with itsprecursor which is a dipeptide, they are localized in retinal fibers innervating thesuprachiasmatic nucleus. Glu is released after stimulation of the optic nerve. One of itsmost important antagonists is NMDA (N-methyl-D-aspartic acid) subtype of Glu receptor.It blocks light phase shifts. Its activation leads to calcium ions influx which can activate NOsynthase in order to produce Nitrogen monoxide. NO is a gaseous neurotransmitter andcan activate Guanylate cyclase or Adenosine diphosphate – ribosyl transferase. NMDAsubtype of postsynaptic Glu receptor has long lasting effects due to Gluneurotransmission. NO has binding affinity to heme-moieties. Hemoglobin acts as aNO-eliminator by competing other targets of NO like guanylate cyclase. The transductionof light signals in SCN requires the formation of NO, which can also permeate cellmembranes and glial cells. Regarding glial cells the possibility that neurons and glia canparticipate in light regulation is raised. Increased NO concentration may lead to therelease of neurotransmitters at synapses of SCN. These transmitters are: Substance Pwhich is localized in retinal fibers and Somatostatin which is endogenous to SCN neuronsand elicits phase shifts similar to those caused by Glu (Ding M.J. et al, 1994).