M4 muscarinic receptors (M4 MR) represent a subfamily of G-protein coupled receptors serving a substantial role in spontaneous locomotor activity regulation, cognition and modulation of cholinergic system. With increasing body of literature discussing the role of M4 MR some controversies arose. Thus, we try here to summarize the current evidence regarding the M4 MR, with the special focus on their role in locomotor activity control. We review the molecular function of M4 MR in specific brain areas implicated in locomotor regulation, and
shortly in other CNS processes that could be connected to locomotor activity. We also focus on brain areas implicated in locomotor activity biorhythm changes like suprachiasmatic nucleus, subparaventricular zone posterior hypothalamic area, striatum and thalamus. Gender-related aspects and differences in locomotor activity in males and females are discussed further.