Abstract
The dorsal striatum forms part of the basal ganglia circuit that is a major regulator of voluntary motor behavior. Dysfunction in this circuit is a critical factor in the pathology of neurological (Parkinson's and Huntington's disease) as well as psychiatric disorders. In this study, we employed in vivo real-time monitoring of multiple unit neural activity (MUA) in the dorsal striatum of freely moving mice. We demonstrate that the striatum exhibits robust diurnal and circadian rhythms in MUA that peak in the night. These rhythms are dependent upon the central circadian clock located in the suprachiasmatic nucleus (SCN) as lesions of this structure caused the loss of rhythmicity measured in the striatum. Nonetheless, chronic treatment of methamphetamine (METH) makes circadian rhythms appear in MUA recorded from the striatum of SCN-lesioned mice. These data demonstrate that the physiological properties of neurons in the dorsal striatum are regulated by the circadian system and that METH drives circadian rhythms in striatal physiology in the absence of the SCN. The finding of SCN-driven circadian rhythms in striatal physiology has important implications for an understanding of the temporal regulation of motor control as well as revealing how disease processes may disrupt this regulation.
Highlights
In mammals, the generation of behavioral and physiological rhythms and the entrainment of these rhythms to the light-dark (LD) cycle are mediated by the suprachiasmatic nucleus (SCN) of the hypothalamus
The mul tiple unit neural activity (MUA) rhythm in the striatum reflects WR activity in untreated SCNi mice, and these rhythms are lost in SCNx mice
We recorded robust diurnal and circadian rhythms in electrical activity in the striatum that peaked during the night and broadly mirrored the rhythms that we measured in WR activity (Fig. 1)
Summary
The generation of behavioral and physiological rhythms and the entrainment of these rhythms to the light-dark (LD) cycle are mediated by the suprachiasmatic nucleus (SCN) of the hypothalamus. It is known that the rhythms of locomotor activity, drinking behavior, and adrenal corticosterone are disrupted in SCN lesioned (SCNx) rodents (Stephan and Zucker, 1972; Moore and Eichler, 1972; Schwartz and Zimmerman, 1991; LeSauter and Silver, 1999). When intact rodents were exposed to METH dissolved in drinking water, the free-running locomotor rhythm was lengthened in a way that was reversible after METH was removed from the drinking water (Honma et al, 1986; Mohawk et al, 2009; Tataroglu et al, 2006). The circadian organization was disturbed and two activity components appeared: one component was free-running (>24 h) and the other was entrained by the LD cycle (Honma et al, 1986; Tataroglu et al, 2006).
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