Sleep and Biological Rhythms

Running Head : Sleep

Sleep

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Sleep

Sleep is a global state , the control mechanisms of which are manifested at every level of biological organization , from genes and intracellular mechanisms to networks of cell populations , and to all central neuronal systems at the organismic level , including those that control movement arousal , autonomic functions , behavior and cognition

Recent genetic findings indicate that the molecular mechanisms that control circadian rhythms , which set the stage for sleep and are inseparable from sleep in a deep

biological sense , are highly conserved phylogenetically . Molecular and behavioral conservation indicates that sleep conferred a selective advantage on ancestral mammals that might persist in modern populations

Prolonged sleep loss impairs temperature control , dietary metabolism and immune function , and leads ultimately to death

In the mammalian nervous system , genetic instructions are expressed at the progressively higher levels of gene transcription , protein synthesis and intracellular events , individual neuronal and neuronal-network dynamics , and ultimately behavior , of which cognition is a specific covert form . In this review , the genetic mechanisms , cellular neurophysiology and subcortical neuronal-population networks are discussed that are involved in sleep (Albrecht , 2002

The circadian pacemaker Starting with the first demonstration of a circadian gene in the fruitfully , genetic approaches have begun to illuminate the intranuclear and cytoplasmic events that are associated with circadian rhythms and sleep . Most notable has been the elucidation of the genetic control of the mammalian circadian pacemaker , which can now explain the near-perfect 24-h rhythmicity of the human circadian clock

Mammalian circadian rhythms are maintained intracellularly by interlocking positive- and negative-feedback control of the transcription (and subsequent translation to protein ) of three period genes (Per1-3 , two cryptochrome genes (Cry , and the Clock and Bmal (brain and muscle ARNT-like 1 ) genes . The products of Clock and Bmal exist as a heterodimer that is a key component of a transcription factor (abbreviated Clock : Bmal ) that promotes the transcription of per and Cry genes by binding to their regulatory DNA sequences (E-box elements . The Per and Cry messenger RNAs are translocated to the cytoplasm for translation to proteins that form complexes that then re-enter the nucleus to exert feedback control on the Clock :Bmal transcription factor . Products of several other genes modulate this intracellular mechanism . For example , the product of the tau (Csnk1e ) gene , casein kinase 1 , phosphorylates per proteins , which affects their translocation between the cytoplasm and the nucleus

Briefly , molecular feedback control of the circadian clock in SCN neurons operates as follows . At the beginning of the organism 's SUBJECTIVE DAY , CIRCADIAN TIME (CT , the transcription and translation of Per and Cry are accelerated by Clock : Bmal heterodimers that have accumulated over the previous subjective night (CT 12-24 . The levels of the Per and Cry complexes peak at the beginning of the organism 's subjective night (CT 12 .Protein complexes that contain the products of the Cry gene exert negative feedback on the Clock :Bmal promoter , thereby slowing the transcription of Per and Cry . At the same time , a protein...