Researchers at Fujita Health University introduced a technique called REPOPS, a form of patterned stimulation in mice designed to mimic key features of electroconvulsive therapy-like neuronal activation. The study, titled Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming, was published in Nature Communications in 2026 and details how the intervention produced measurable behavioral and cellular changes in animal subjects.

Mice subjected to REPOPS stimulation demonstrated increased locomotor activity and reduced depression-like behavior compared to baseline measurements. The behavioral effects depended on the duration of stimulation: three days of REPOPS stimulation caused only transient changes in the mice, while ten days of REPOPS stimulation resulted in a stable dematuration state that persisted for over a month after the intervention ended.

At the cellular level, REPOPS stimulation induced a state of cellular dematuration in adult neurons, with gene expression patterns resembling those seen in early postnatal development. Genome-wide chromatin mapping revealed widespread and persistent changes in chromatin accessibility in the mice following the stimulation protocol. Neurons following REPOPS exhibited gene expression patterns characteristic of the G2/M phase of the cell cycle. At the nuclear level, these neurons displayed hallmarks of mitosis, including histone phosphorylation, disruption of the nuclear lamina, and chromatin condensation.

The researchers also examined the role of specific cell cycle proteins in the process. Mice lacking Cyclin B showed less nuclear reprogramming and fewer behavioral changes following REPOPS stimulation, indicating that the protein plays a functional role in the observed cellular and behavioral response.

REPOPS stimulation produced a patterned shift in how neurons encode information, suppressing spatial coding while enhancing speed-related coding. This shift in neuronal coding patterns persisted for over two weeks following the stimulation protocol, suggesting that the cellular changes produced lasting alterations in neural circuit function.

Fujita Health University Professor Tsuyoshi Miyakawa described the findings as revealing a previously unexamined mechanism. "Nuclear reprogramming - the ability of neurons to fundamentally reshape their own identity - is a candidate mechanism we had not previously considered," Miyakawa said.

To test whether the cellular patterns observed in mice corresponded to findings in humans, the researchers conducted a reanalysis of postmortem brain RNA-seq data from patients with mood disorders. The analysis showed that ECT-treated individuals exhibited a similar immature-like gene expression pattern in the dentate gyrus compared to non-ECT-treated patients, linking the animal model findings to clinical observations.

Researchers propose that the dematured cellular state induced by the stimulation represents an intermediate state of high plasticity, in which adult neurons temporarily revert to a more developmentally flexible condition. "These findings provide a new cellular framework for thinking about how durable changes in neural function can arise, and they offer a potential route to improved therapies," Miyakawa said in a written statement accompanying the publication.

Electroconvulsive therapy remains one of the most effective treatments for severe depression, yet the cellular mechanisms underlying its durability have remained unclear. The REPOPS findings suggest that the treatment may work by temporarily pushing adult neurons into a dematured state associated with heightened plasticity, a mechanism the researchers characterized as nuclear reprogramming. The correspondence between the mouse data and postmortem human brain tissue analyzed in the study provides a potential bridge between animal models and clinical observation, though further research would be needed to establish causal links in human patients.