Abstract
BackgroundMammals can adapt to changing light/dark conditions by advancing or delaying their circadian clock phase. Light pulses evoke changes in gene expression and neuronal activity in the suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system. Alterations in neuronal activity are partially mediated by changes in synaptic vesicle (SV) fusion at the presynaptic membrane, which modulates release of neurotransmitters.MethodsMale synaptophysin (Syp) knock-out and littermate control wild type mice were tested in an Aschoff type I resetting paradigm. Additionally, gene expression of cFos, Per1 and Per2 was assessed in the SCN. Finally, complexes between the synaptic vesicle proteins Syp and synaptobrevin (Syb) were studied in order to correlate behavior with protein complexes at synaptic vesicles.ResultsHere we show that mice lacking Syp, a modulator of neurotransmitter release, are defective in delaying clock phase. In contrast, clock phase advances as well as clock period are normal in Syp-/- knock-out mice. This correlates with the formation of Syp/Syb complexes.ConclusionsOur findings suggest that Syp is involved specifically in the response to a nocturnal light pulse occurring in the early night. It appears that the SV component Syp is critically involved in the delay portion of the resetting mechanism of the circadian clock.
Highlights
Mammals can adapt to changing light/dark conditions by advancing or delaying their circadian clock phase
Light signals are transmitted from the retina via the retinohypothalamic tract to a subset of suprachiasmatic nuclei (SCN) neurons leading to the activation of several signaling pathways that evoke chromatin remodeling and the induction of immediate early genes and clock genes [2]
Spreading of this information from light receptive SCN neurons to their neighbors eventually evokes a change of clock phase in the SCN, leading to a behavioral change that can be readily observed as a change in onset of wheel running activity [3]
Summary
Mammals can adapt to changing light/dark conditions by advancing or delaying their circadian clock phase. How the molecular clock drives secretion of neurotransmitters is not clear, a number of gene and protein profiling studies identified several genes [5] and proteins [6] in the SCN to be expressed in a time of day dependent manner Among these genes and proteins, factors involved in the function of synaptic vesicles (SVs) are of particular interest, because SVs are responsible for the transmission of information from one cell to another in the brain. The action potential triggers SV exocytosis into the synaptic cleft, where the released neurotransmitters activate postsynaptic receptors and elicit a cellular response [7] In this process, the regulation of the filling state and fusion of SVs with the plasma membrane and their endocytic retrieval are critical. Proteomic analysis revealed a role of SV cycling in sustaining the SCN circadian clock [10]
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