Abstract
The deletion of M4 muscarinic receptors (MRs) changes biological rhythm parameters in females. Here, we searched for the mechanisms responsible for these changes. We performed biological rhythm analysis in two experiments: in experiment 1, the mice [C57Bl/6NTac (WT) and M4 MR −/− mice (KO)] were first exposed to a standard LD regime (12/12-h light/dark cycle) for 8 days and then subsequently exposed to constant darkness (for 24 h/day, DD regime) for another 16 days. In experiment 2, the mice (after the standard LD regime) were exposed to the DD regime and to one light pulse (zeitgeber time 14) on day 9. We also detected M1 MRs in brain areas implicated in locomotor biological rhythm regulation. In experiment 1, the biological rhythm activity curves differed: the period (τ, duration of diurnal cycle) was shorter in the DD regime. Moreover, the day mean, mesor (midline value), night mean and their difference were higher in KO animals. The time in which the maximal slope occurred was lower in the DD regime than in the LD regime in both WT and KO but was lower in KO than in WT mice. In experiment 2, there were no differences in biological rhythm parameters between WT and KO mice. The densities of M1 MRs in the majority of areas implicated in locomotor biological rhythm were low. A significant amount of M1 MR was found in the striatum. These results suggest that although core clock output is changed by M4 MR deletion, the structures involved in biological rhythm regulation in WT and KO animals are likely the same, and the most important areas are the striatum, thalamus and intergeniculate leaflet.
Highlights
The generation of the rhythmic pattern controlling locomotion is formed by the activity of intrinsically oscillating interneurons in the spinal cord (Wyartt 2018)
The mice were first exposed to a standard LD regime for eight consecutive days and exposed to constant darkness for the other sixteen days
We have shown that the biological rhythm activity curves differed after switching to the DD regime
Summary
The generation of the rhythmic pattern controlling locomotion is formed by the activity of intrinsically oscillating interneurons in the spinal cord (Wyartt 2018). Researchers agree that locomotion is generated centrally in the spinal cord by circuits referred to as central pattern generators (CPGs, see Table 1 for list of abbreviations). In addition to on-demand triggering of these commands to meet the homeostatic needs of the organism, locomotion itself reveals a diurnal pattern directed by a series of pacemakers. SCN has been shown to be innervated by cholinergic nerves (Hut and Van der Zee 2011) but does not have to be necessarily intrinsically cholinergic (van den Pol and Tsujimoto 1985). It receives cholinergic projections from basal forebrain and
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