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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

Forniceal deep brain stimulation improves memory in Rett syndrome mice by promoting the maturation of newborn hippocampal neurons

  • Qi Wang1,2
  • Bin Tang1,2
  • Zhenyu Wu1,2
  • Huda Y. Zoghbi1,2,3,4,5,6
  • Jianrong Tang1,2
6 affiliations
  1. 1Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030
  2. 2Department of Pediatrics, Division of Neurology, Baylor College of Medicine, Houston, TX 77030
  3. 3Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
  4. 4Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030
  5. 5Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030
  6. 6HHMI, Baylor College of Medicine, Houston, TX 77030
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Abstract

Deep brain stimulation (DBS) is associated with an increase in hippocampal neurogenesis and memory benefits, but the causal mechanism is unclear. Here, we use a mouse model of Rett syndrome, a severe learning disability syndrome caused by MECP2 loss of function, to find that DBS promotes the maturation and integration of newborn dentate granule cells (DGCs) into the neural circuit. Suppressing hippocampal neurogenesis prevented DBS from improving learning and memory. Newborn methyl-CpG-binding protein 2 (MeCP2)-deficient DGCs in Rett syndrome mice showed attenuated development and synaptic dysfunction, but DBS rescued DGC dendritic arborization, synaptogenesis, and long-term synaptic plasticity. DBS achieves this, at least in part, by increasing the protein level and shifting the phosphorylation of potassium chloride cotransporter 2, thereby restoring the conversion of GABAergic signaling from depolarization to hyperpolarization, a process that is otherwise delayed by MeCP2 deficiency. This study pinpoints one mechanism by which chronic DBS promotes neuronal maturation and enhances memory.

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Cite

BibTeXRIS
BibTeX
@article{wang2026forniceal,
  title = {{Forniceal deep brain stimulation improves memory in Rett syndrome mice by promoting the maturation of newborn hippocampal neurons}},
  author = {Qi Wang and Bin Tang and Zhenyu Wu and Huda Y. Zoghbi and Jianrong Tang},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2535887123},
  url = {https://doi.org/10.1073/pnas.2535887123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Forniceal deep brain stimulation improves memory in Rett syndrome mice by promoting the maturation of newborn hippocampal neurons
AU  - Qi Wang
AU  - Bin Tang
AU  - Zhenyu Wu
AU  - Huda Y. Zoghbi
AU  - Jianrong Tang
PY  - 2026
DA  - 2026/10/28
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2535887123
UR  - https://doi.org/10.1073/pnas.2535887123
AB  - Deep brain stimulation (DBS) is associated with an increase in hippocampal neurogenesis and memory benefits, but the causal mechanism is unclear. Here, we use a mouse model of Rett syndrome, a severe learning disability syndrome caused by MECP2 loss of function, to find that DBS promotes the maturation and integration of newborn dentate granule cells (DGCs) into the neural circuit. Suppressing hippocampal neurogenesis prevented DBS from improving learning and memory. Newborn methyl-CpG-binding protein 2 (MeCP2)-deficient DGCs in Rett syndrome mice showed attenuated development and synaptic dysfunction, but DBS rescued DGC dendritic arborization, synaptogenesis, and long-term synaptic plasticity. DBS achieves this, at least in part, by increasing the protein level and shifting the phosphorylation of potassium chloride cotransporter 2, thereby restoring the conversion of GABAergic signaling from depolarization to hyperpolarization, a process that is otherwise delayed by MeCP2 deficiency. This study pinpoints one mechanism by which chronic DBS promotes neuronal maturation and enhances memory.
SN  - 0027-8424
SN  - 1091-6490
ER  -