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AI Summary of Peer-Reviewed Research

This page presents an AI-generated summary of a published research paper. The original authors did not write or review this article. [See full disclosure ↓]

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Brief electrical stimulation induced ketamine-like plasticity in human neurons

Neuroscience research
Photo by Bioscience Image Library by Fayette Reynolds on Unsplash · Unsplash License
Research area:NeuroscienceNeuroscience and Neural EngineeringCellular and Molecular Neuroscience

What the study found

A single brief low-frequency, low-intensity electrical stimulation session produced long-lasting, ketamine-like structural and molecular changes in human induced pluripotent stem cell-derived dopaminergic neurons.

Why the authors say this matters

The authors conclude that these findings support low-frequency, low-intensity electrical stimulation as a neuromodulation approach targeting dopaminergic circuits in major depressive disorder and treatment-resistant depression. They also suggest it may help address stress hormone-related neuronal impairments.

What the researchers tested

The researchers applied brief biphasic low-frequency, low-intensity electrical stimulation to human iPSC-derived mesencephalic dopaminergic neurons using a custom culture-compatible stimulator. They measured structural plasticity three days later and used pharmacological blockers, quantitative PCR, and Western blot analyses to examine calcium influx, BDNF-TrkB-ERK-mTOR signaling, and dopamine D3 auto-receptors.

What worked and what didn't

A single 1-hour session at 4 mA increased maximal dendrite length, primary dendrite number, and soma area, with effects comparable to 1 μM ketamine. The stimulation rapidly increased ERK and p70-S6K phosphorylation, and blocking L-type voltage-gated calcium channels, TrkB, or mTOR prevented the structural remodeling. Increased dopamine D3 auto-receptor mRNA was also observed, and antagonizing this receptor attenuated the stimulation-induced plasticity. In cortisol-treated neurons, the stimulation fully reversed dendritic hypotrophy and soma shrinkage.

What to keep in mind

The abstract describes an in-vitro study in human iPSC-derived dopaminergic neurons, so the findings are limited to that model. The summary provided does not describe additional limitations beyond the experimental scope.

Key points

  • A single 1-hour low-frequency, low-intensity electrical stimulation session produced ketamine-like changes in human dopaminergic neurons.
  • The stimulation increased dendrite length, primary dendrite number, and soma area.
  • Blocking L-type calcium channels, TrkB, or mTOR prevented the structural remodeling.
  • The stimulation increased dopamine D3 auto-receptor mRNA, and receptor antagonism reduced the effect.
  • In cortisol-treated neurons, the stimulation reversed dendritic hypotrophy and soma shrinkage.

Disclosure

Research title:
Brief electrical stimulation induced ketamine-like plasticity in human neurons
Authors:
Giulia Sofia Marcotto, Michela Borghetti, Jonida Bitraj, Laura Cavalleri, Mauro Serpelloni, Michele Zoli, Maurizio Memo, Emilio Sardini, Ginetta Collo
Institutions:
University of Brescia, University of Modena and Reggio Emilia
Publication date:
2026-04-05
DOI:
10.1016/j.neuropharm.2026.110964
OpenAlex record:
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Image credit:
Photo by Bioscience Image Library by Fayette Reynolds on Unsplash · Unsplash License
AI provenance: This post was generated by OpenAI. The original authors did not write or review this post.

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