Colloquium on September 27, 2010

Michael Hastings
MRC, Laboratory of Molecular Biology,   Division of Neurobiology

Pacemaking and synchronisation in the brains circadian centre, the suprachiasmatic nucleus

Circadian rhythms, the most obvious of which is the sleep/wake cycle, are daily rhythms of physiology and behaviour that persist in individuals when they are deprived of external time cues.  Such rhythms are thus driven by internal biological clocks with an intrinsic period of approximately (circa-) one day.  The suprachiasmatic nucleus of the hypothalamus (SCN) is the principal circadian pacemaker of the brain and it co-ordinates the bodys myriad circadian cycles, ensuring that internal time is adaptively matched to external, solar time.  Loss of temporal adaptation compromises mental and physical performance, as well as long term health.  The core element of the circadian timing mechanism is a series of inter-linked transcriptional/ post-translational feedback loops, in which the activity of circadian clock genes (Per1, Per2, Cry1 and Cry2) is periodically suppressed by the feedback actions of the proteins that they encode.  This presentation will consider how the period of the SCN circadian pacemaker is determined by the stability of the Per and Cry proteins, individually and by their interactions, and how pharmacological regulation of Per stability can alter the circadian organisation of behaviour.  In addition to these intra-cellular mechanisms, the SCN pacemaker is dependent upon inter-cellular processes, insofar as signalling between SCN neurons is necessary to both sustain the intra-cellular feedback loops and maintain synchrony across the population of SCN neurons.  This presentation will review the central role of neuropeptidergic signalling as the mediator of this circuit-level, temporal communication.  In conclusion, the circadian timing mechanism may be of interest and utility in the analysis of basic processes of biological timing, from events occurring within the cell and events that occur between cells.