Abstract
The suprachiasmatic nuclei (SCN) coordinate the daily sleep-wake cycle by generating a circadian rhythm in electrical impulse frequency. While period and phase of the SCN rhythm have been considered as major output parameters, we propose that the waveform of the rhythm of the SCN also has significance. Using implanted micro-electrodes, we recorded SCN impulse frequency in freely moving mice and manipulated its circadian waveform by exposing mice to light-dark (LD) cycle durations ranging from 22 hours (LD 11∶11) to 26 hours (LD 13∶13). Adaptation to long T-cycles (>24 h) resulted in a trough in electrical activity at the beginning of the night while in short T-cycles (<24 h), SCN activity reached a trough at the end of night. In all T-cycle durations, the intensity of behavioral activity was maximal during the trough of SCN electrical activity and correlated negatively with increasing levels of SCN activity. Interestingly, small changes in T-cycle duration could induce large changes in waveform and in the time of trough (about 3.5 h), and accordingly in the timing of behavioral activity. At a smaller timescale (minutes to hours), we observed a negative correlation between SCN activity and behavioral activity, and acute silencing of SCN neurons by tetrodotoxin (TTX) during the inactive phase of the animal triggered behavioral activity. Thus, the SCN electrical activity levels appear crucially involved in determining the temporal profile of behavioral activity and controls behavior beyond the circadian time domain.
Highlights
Twenty four hour rhythms in physiology and behavior are ubiquitous in the animal kingdom, and are an evolutionary adaptation to the environmental rhythms caused by the rotation of the earth
suprachiasmatic nuclei (SCN) electrical impulse frequencies were successfully recorded in animals that were entrained to light-dark (LD) cycles of 24 hours (T = 24 h), to shorter T-cycles with a minimum of 22 hours (T = 22 h), and to longer T-cycles with a maximum of 26 hours (T = 26 h, Figs. 1A and B)
Under T = 24 h, low electrical activity levels were reached during the dark part of the LD cycle, and high electrical activity occurred during the light part of the LD cycle
Summary
Twenty four hour rhythms in physiology and behavior are ubiquitous in the animal kingdom, and are an evolutionary adaptation to the environmental rhythms caused by the rotation of the earth. The hypothalamic suprachiasmatic nuclei (SCN) function as a master clock that coordinate a multitude of rhythmic processes in the body. The rhythms of the SCN are explained by the interaction between an intra-neuronal molecular network involving circadian genes and their products and intercellular communication within the SCN neuronal network [1,2]. While the intracellular circadian molecular network is rhythmic in many peripheral tissues, the SCN is necessary for coordinating these rhythms and for driving the 24 hour rhythm in behavioral activity levels and sleep [3,4,5,6]. Several output factors of the SCN are triggered and released by electrical activity of SCN neurons, including arginine vasopressin, gamma-amino butyric acid, glutamate, prokineticin, cardiotrophin-like cytokine and vasoactive intestinal peptide [7,8,9,10,11,12]
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