Immotile cilia sense extracellular signals such as fluid flow, but whether Ca²⁺ plays a role in flow sensing has been unclear. Here, we examined the role of ciliary Ca²⁺ in the flow sensing that initiates the breaking of left-right (L-R) symmetry in the mouse embryo. Intraciliary and cytoplasmic Ca²⁺ transients were detected in the crown cells at the node. These Ca²⁺ transients showed L-R asymmetry, which was lost in the absence of fluid flow or the PKD2 channel. Further characterization allowed classification of the Ca²⁺ transients into two types: cilium-derived, L-R-asymmetric transients (type 1) and cilium-independent transients without an L-R bias (type 2). Type 1 intraciliary transients occurred preferentially at the left posterior region of the node, where L-R symmetry breaking takes place. Suppression of intraciliary Ca²⁺ transients delayed L-R symmetry breaking. Our results implicate cilium-derived Ca²⁺ transients in crown cells in initiation of L-R symmetry breaking in the mouse embryo.

The insular cortex (IC) participates in diverse complex brain functions, including social function, yet their cellular bases remain to be fully understood. Using microendoscopic calcium imaging of the agranular insular cortex (AI) in mice interacting with freely moving and restrained social targets, we identified 2 subsets of AI neurons—a larger fraction of “Social-ON” cells and a smaller fraction of “Social-OFF” cells—that change their activity in opposite directions during social exploration. Social-ON cells included those that represented social investigation independent of location and consisted of multiple subsets, each of which was preferentially active during exploration under a particular behavioral state or with a particular target of physical contact. These results uncover a previously unknown function of AI neurons that may act to monitor the ongoing status of social exploration while an animal interacts with unfamiliar conspecifics.

Significance: Voltage-gated sodium channels (Na_V) are known to form clusters at the membranes of excitable cells; however, what governs their transport is largely unknown. We found that the endoplasmic reticulum (ER) andcis-Golgi associated ubiquitin ligase really interesting new gene (RING) finger protein 121 (RNF121) mediates the degradation and membrane localization of Na_V. This apparent quality control of Na_Vensures the transport of properly folded channels to the membranes of excitable cells. To our knowledge, this is the first pathologically relevant identification of a voltage-gated ion channel as a substrate for ER-associated protein degradation, whose degradation is governed by an ER- and Golgi-associated E3-ubiquitin ligase.

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-β cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

In the brain, spatial information is represented by neurons that fire when an animal is at specific locations, including place cells in hippocampus and grid cells in entorhinal cortex. But how this information is processed in downstream brain regions still remains elusive. Using chronic Ca²⁺ imaging, we examined the activity of neurons in anterior cingulate cortex (ACC), a brain region implicated in memory consolidation, and found neurons that fire in a manner consistent with the properties of place cells. While the ACC place cells showed stability, location and context specificity similar to the hippocampal counterparts, they also have unique properties. Unlike hippocampal place cells that immediately formed upon exposure to a novel environment, ACC place cells increased over days. Also, ACC place cells tend to have additional place fields whereas typical hippocampal place cells have only one. Hippocampal activity is required for the formation of ACC place cells, but once they are established, hippocampal inactivation did not have any impact on ACC place cell firing. We thus identified features of ACC place cells that carry spatial information in a unique fashion.

In the hippocampus, spatial and nonspatial information are jointly represented as a neural map in which locations associated with salient features are over‐represented by increased densities of relevant place cells. Although we recently demonstrated that experience‐dependent establishment of these disproportionate maps is governed by selective stabilization of salient place cells following their conversion from non‐place cells, the underlying mechanism for pre‐established map reorganization remained to be understood. To this end, we investigated the changes in CA1 functional cellular maps imaged using two‐photon calcium imaging in mice performing a reward‐rearrangement task in virtual reality. Mice were pre‐trained on a virtual linear track with a visual landmark and a reward in two distinct locations. Then, they were re‐trained on the same track with the exception that the location of reward was shifted to match the landmark location. We found that, in contrast to de novo map formation, robust map reorganization occurred through parallel coordination of new place field formation, lateral shifting of existing place fields, and selective stabilization of place fields encoding salient locations. Our findings demonstrate that intricate interplay between multiple forms of cellular dynamics enables rapid updating of information stored in hippocampal maps.