Research Highlight:

Behaving by Consensus...

Original Research Article:
CM Ciarleglio, KL Gamble, JC Axley, BR Strauss, JY Cohen, CS Colwell and DG McMahon (2008).  Population Encoding by Circadian Clock Neurons Organizes Circadian Behavior. Journal of Neuroscience. 29 (6): 1670-6.

Behaving by consensus

Circadian rhythms are a nearly ubiquitous feature of life on earth, and are controlled in mammals by the suprachiasmatic nuclei of the hypothalamus (SCN).  Since its identification as the primary clock more than 30 years ago, how neurons within the SCN control circadian physiology and behavior has been a mystery.  In a study recently published in the Journal of Neuroscience, Ciarleglio and colleagues demonstrated how neurons within the SCN worked together as a population to control circadian behavioral rhythms.

Circadian rhythms are controlled in mammalian tissues by a set of clock genes that include some that are expressed robustly during the daytime (e.g. Period1).  Neurons within the SCN are thought to be synchronized by vasoactive intestinal polypeptide (VIP).  In this study, the authors used a dual-transgenic reporter mouse with a short half-life Period1 promoter-driven green fluorescent protein (Per1::GFP) and a knockout for VIP to study the relationship between neuronal rhythm synchrony ex vivo and robust behavioral rhythmicity in vivoPer1::GFP mice wildtype, heterozygous or knockout for VIP were behaviorally characterized in a light-dark cycle or in constant darkness, then their brains were extracted and their SCN imaged using time-lapse confocal fluorescent microscopy to observe the expression of GFP ex vivo.

Behaviorally, VIP-/- Per1::GFP mice were arrhythmic, and more phase advanced than VIP+/- and VIP+/+ mice, which were found to exhibit strongly rhythmic behavior with normal behavior onsets in LD and in DD.  These results support previous reports that VIP-/- mice had disrupted behavioral rhythms.  Ex vivo (how the authors refer to acute in vitro culture) rhythms were also disrupted in VIP-/- mice, such that they expressed much less neuronal synchrony in the phase of Per1::GFP expression than VIP+/- and VIP+/+ mice.  The authors statistically correlated the degree of neuronal synchrony within an SCN to the power of the same animal’s behavioral rhythm, and demonstrated a significant relationship between the two measurements.  They found that as the amount of neuronal phase variance increased ex vivo, the power of the behavioral circadian rhythm decreased, suggesting that the population of neurons as a whole controlled behavioral output.

The authors also reported two other novel findings.  First, the proportion of rhythmic neurons in VIP-/- mice was not statistically different from VIP+/- and VIP+/+ mice.  This is significant because previous studies had suggested that a lack of VIP led to an overall lack of circadian rhythmicity.  Instead, the results of this study suggest that it is neuronal asynchrony that results in behavioral arrhythmicity.  Second, an advance in Per1::GFP expression correlated to the advance of behavioral onset seen in VIP-/- mice, accounting for this strange phenomenon.

This study is significant in that it demonstrated that neurons within the SCN encode behavior as a population, not unlike the population coding seen in the voluntary motor system where the direction of limb movement is controlled by an average population vector in the motor cortex.