Deep brain stimulation improves new neuron maturation for memory

by Graciela Gutierrez, Baylor College of Medicine

edited by Gaby Clark, reviewed by Robert Egan

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Deep brain stimulation (DBS) has traditionally been used to treat movement disorders and more recently some mental health disorders such as certain forms of depression, but research has suggested it can affect learning and memory as well.

Baylor College of Medicine researchers studying Rett syndrome at the Duncan Neurological Research Institute (NRI) at Texas Children's Hospital have found that DBS targeted to a certain area of the brain can improve learning and memory in a mouse model of Rett syndrome, offering new insights into the brain mechanisms involved in this disorder and potential future treatment targets.

The findings, published in the Proceedings of the National Academy of Sciences, show that DBS promotes the development of newborn neurons into hippocampal neural circuits. In Rett syndrome, MeCP2 gene deficiency impairs the development of newborn neurons, resulting in reduced dendritic formation and impaired synaptic function among other developmental dysfunctions.

Tracing disrupted memory circuits

Dr. Jianrong Tang, associate professor of pediatric neurology at Baylor and a neuroscientist at the Duncan NRI, has spent years investigating how neural circuits support cognitive functions such as learning and memory. Working with Rett syndrome mouse models, Tang and collaborators examined how disruptions in these circuits contribute to cognitive difficulties.

"We found that the Rett syndrome model showed impaired communication between neurons in the hippocampus. Signal transmission between neurons was disrupted and their ability to strengthen connections—synaptic plasticity, a process important for memory formation—was also altered," Tang said.

In earlier research, the team showed that two weeks of daily DBS targeting the fornix, a pathway connecting the hippocampus with other brain regions, rescued learning and memory performance in the mouse models of intellectual disability disorders (IDDs) including Rett syndrome. DBS treatment also increased the production of new neurons in the brain.

New neurons drive memory gains

In the latest study, the researchers focused on whether newly generated neurons were necessary for these benefits. They were able to block the production of new neurons and found that there was no longer memory improvement with DBS. They also showed that the new neurons needed time to mature before supporting memory improvements.

"DBS helped restore the morphological structure of newborn neurons that did not have the MECP2 protein," Tang said. "DBS also improved communication between neurons and helped rebalance the excitatory and inhibitory signaling, two processes that must be in balance for healthy brain activity."

KCC2 links stimulation to neuron maturation

So what are the underlying molecular mechanisms causing these improvements?

"The protein KCC2 is reduced by MeCP2 loss. KCC2 is important because it helps regulate the functional shift of the neurotransmitter GABA from excitatory to inhibitory when developing properly," Tang said. "If KCC2 is not functioning properly then GABAergic switching from excitation to inhibition is delayed. As a result, newborn neuron maturation is postponed, which may hinder learning and memory. We found that activating KCC2 in the Rett syndrome model mimicked the DBS effect and improved memory performance."

Tang emphasized that these findings are currently only in a mouse model and additional studies will be needed to determine whether similar approaches are safe and effective in those living with Rett syndrome.

"By identifying how neural circuit stimulation, neuron maturation and molecular signaling interact, we have provided a foundation for exploring new strategies to improve cognitive function in Rett syndrome and, hopefully, other IDDs," Tang said.

Other contributing researchers include Drs. Qi Wang, Bin Tang, Zhenyu Wu and Huda Zoghbi, all with Baylor College of Medicine and the Duncan NRI.

Publication details

Jianrong Tang et al., Forniceal deep brain stimulation improves memory in Rett syndrome mice by promoting the maturation of newborn hippocampal neurons, Proceedings of the National Academy of Sciences (2026). DOI: 10.1073/pnas.2535887123

Journal information: Proceedings of the National Academy of Sciences

Key medical concepts

Rett SyndromeDeep Brain Stimulation

Clinical categories

NeurologyPediatrics Provided by Baylor College of Medicine Who's behind this story?

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