The circadian clock enables organisms to synchronize biochemical and physiological processes over a 24 hr period. Natural changes in lighting conditions, as well as artificial disruptions like jet lag or shift work, can advance or delay the clock phase to align physiology with the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian timekeeping and resetting rely on both membrane depolarization and intracellular second-messenger signaling. Voltage-gated calcium channels (VGCCs) facilitate calcium influx in both processes, activating intracellular signaling pathways that trigger Period (Per) gene expression. However, the precise mechanism by which these processes are concertedly gated remains unknown. Our study in mice demonstrates that cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and regulates phase shifts of the circadian clock. We observed that knocking down Cdk5 in the SCN of mice affects phase delays but not phase advances. This is linked to uncontrolled calcium influx into SCN neurons and an unregulated protein kinase A (PKA)-calcium/calmodulin-dependent kinase (CaMK)-cAMP response element-binding protein (CREB) signaling pathway. Consequently, genes such as Per1 are not induced by light in the SCN of Cdk5 knock-down mice. Our experiments identified Cdk5 as a crucial light-modulated kinase that influences rapid clock phase adaptation. This finding elucidates how light responsiveness and clock phase coordination adapt activity onset to seasonal changes, jet lag, and shift work.

The emergence of symbolic thinking has been proposed as a dominant cognitive criterion to distinguish humans from other primates during hominisation. Although the proper definition of a symbol has been the subject of much debate, one of its simplest features is bidirectional attachment: the content is accessible from the symbol, and vice versa. Behavioural observations scattered over the past four decades suggest that this criterion might not be met in non-human primates, as they fail to generalise an association learned in one temporal order (A to B) to the reverse order (B to A). Here, we designed an implicit fMRI test to investigate the neural mechanisms of arbitrary audio–visual and visual–visual pairing in monkeys and humans and probe their spontaneous reversibility. After learning a unidirectional association, humans showed surprise signals when this learned association was violated. Crucially, this effect occurred spontaneously in both learned and reversed directions, within an extended network of high-level brain areas, including, but also going beyond, the language network. In monkeys, by contrast, violations of association effects occurred solely in the learned direction and were largely confined to sensory areas. We propose that a human-specific brain network may have evolved the capacity for reversible symbolic reference.