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Assaying Circuit Specific Regulation of Adult Hippocampal Neural Precursor Cells
Published on: July 24, 2019
Repetitive neuronal activation regulates cellular maturation state via nuclear reprogramming
Tomoyuki Murano1, Hideo Hagihara1, Katsunori Tajinda2
1Division of Systems Medical Science, Center for Medical Science, Fujita Health University, Toyoake, Japan.
Nature Communications
|July 17, 2026
Summary
Repeated brain stimulation, like electroconvulsive therapy (ECT), induces long-lasting cellular changes in the brain. This nuclear reprogramming may explain how these therapies effectively treat psychiatric disorders.
Area of Science:
- Neuroscience
- Cellular Biology
- Psychiatry
Background:
- Neural stimulation therapies like electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are effective for psychiatric disorders.
- The precise cellular mechanisms underlying the efficacy of these brain stimulation techniques remain largely unknown.
Purpose of the Study:
- To investigate the cellular-level mechanisms of electroconvulsive therapy (ECT) using a mouse model.
- To identify molecular and cellular changes induced by chronic neuronal stimulation relevant to psychiatric treatment.
Main Methods:
- Modeled ECT using repeated optogenetic neuronal stimulation in the mouse dentate gyrus.
- Observed behavioral changes and analyzed cellular alterations, including nuclear structure and gene expression.
- Investigated the role of Cyclin B, a G2/M phase regulator, by using knockout models.
Main Results:
- Observed ECT-relevant behavioral changes, including reduced depression-like behavior and increased locomotor activity.
- Identified a long-term stable cellular state characterized by nuclear structural changes and gene expression resembling the G2/M cell cycle phase.
- Found that altered neural coding of navigational information persisted for over a month.
- Demonstrated that Cyclin B knockout attenuated some behavioral and cellular effects of stimulation.
Conclusions:
- Chronically repeated brain stimulation induces plasticity in cellular states, leading to long-term changes.
- Revealed a novel form of stimulus-regulated nuclear reprogramming with potential therapeutic applications in psychiatry.
- Suggests that targeting cell cycle regulators like Cyclin B could modulate the effects of brain stimulation therapies.
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