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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
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 Brescia, University of Brescia, University of Brescia, University of Brescia, University of Brescia, University of Brescia, 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
AI provenance: This post was generated by OpenAI. The original authors did not write or review this post.

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