The circadian rhythmicity displayed by motor behavior of mice: activity at night and rest during the day; and the associated changes in the sensory input are reflected by cyclic synaptic plasticity in the whisker representations located in the somatosensory (barrel) cortex. It was not clear whether diurnal rhythmic changes in synapse density previously observed in the barrel cortex resulted from changes in the activity of the animals, from daily light/dark (LD) rhythm or are driven by an endogenous clock. These changes were investigated in the barrel cortex of C57BL/6 mouse strain kept under LD 12 : 12 h conditions and in constant darkness (DD). Stereological analysis of serial electron microscopic sections was used to assess numerical density of synapses. In mice kept under LD conditions, the total density of synapses and the density of excitatory synapses located on dendritic spines was higher during the light period (rest phase). In contrast, the density of inhibitory synapses located on dendritic spines increased during the dark period (activity phase). Under DD conditions, the upregulation of the inhibitory synapses during the activity phase was retained, but the cyclic changes in the density of excitatory synapses were not observed. The results show that the circadian plasticity concerns only synapses located on spines (and not those on dendritic shafts), and that excitatory and inhibitory synapses are differently regulated during the 24 h cycle: the excitatory synapses are influenced by light, whilst the inhibitory synapses are driven by the endogenous circadian clock.
Investigations on the effects of the 5-HT agonists and antagonists on the phase of the circadian locomotor activity rhythm of animals kept in constant light conditions (LL) are rare. Therefore the influence of R-(+)-OH-DPAT (5-HT 1A receptors agonist) and metergoline (5-HT 1/2/7 receptors antagonist) on the phase shift of the locomotor-activity rhythm alone and when combined with dark pulses in mice kept in LL are examined. The results indicate that 8-OH-DPAT administered independently at 12.00CT (Circadian Time) shifted the phase of the circadian rhythm and reinforced the effect of dark pulses on this parameter. 12.00CT was defined arbitrarily as the onset of locomotor activity in constant conditions. Metergoline diminished the phase shifts after dark pulses compared to 8-OH-DPAT. The influence of the serotonin agonist showed that serotonin can reinforce the phase shifting effect of the locomotor activity rhythm after dark pulses in LL condition.
IntroductionGalanthamine, a long-acting, centrally-active competitive acetylcholinesterase (AChE) inhibitor and well-tolerated drug is currently used in the symptomatic of Alzheimer's disease. In mouse brain it reaches maximum inhibition of AChE amounting to about 91 % within lhr after the intraperitoneal injection of 5 mg/kg and still after 12hr 63% inhibition of the enzyme was assumed (Bickel et al., 1991).Our previous investigation indicated that galanthamine affects the circadian wheel-running activity rhythm in mice at LL and DD condition.The aim of this study was to determine if this drug affects the circadian wheel-running activity rhythm in mice with lesioned SCN.
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