Neurodevelopmental Disorders: Deep Brain Stimulation Alleviates

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RESEARCH HIGHLIGHTS Nature Reviews Neurology 11, 666 (2015); published online 3 November 2015; doi:10.1038/nrneurol.2015.207

NEURODEVELOPMENTAL DISORDERS Deep brain stimulation alleviates hippocampal memory deficit in a mouse model of Rett syndrome Deep brain stimulation (DBS) of the fornix and colleagues from the Baylor College “This might be the first study to show can increase neural activity and mitigate of Medicine and the Jan and Dan Duncan that neuromodulation improves the memory deficit in a mouse model of Rett Neurological Research Institute (Houston, cognitive deficits and plasticity in an syndrome, according to new research TX, USA) set out to study the effects of animal model of intellectual disability published in Nature. “These findings forniceal DBS on hippocampus-dependent disorder,” comments Zoghbi. Currently, provide hope that DBS might enhance the memory in female Mecp2+/– mice, a only symptomatic treatment is available cognitive abilities of individuals with Rett well-characterized mouse model of Rett for Rett syndrome and other intellectual syndrome,” comment Huda Zoghbi and syndrome that reproduces the broad disability disorders. Jianrong Tang, who led the study. phenotype of the disorder, including The mechanisms through which DBS Forniceal DBS has previously been cognitive deficits and motor dysfunction. improved hippocampal learning remain reported to improve memory in healthy The investigators applied DBS in the elusive. “We found that DBS in the fornix individuals, and to retard the progression fornix of awake, freely moving mice, using increased hippocampal neurogenesis, of Alzheimer disease in early trials. a stimulation frequency similar to that which has been demonstrated to Inspired by these findings, Zoghbi, Tang used in humans. Stimulation intensities contribute to learning and memory,” says were adjusted individually for each mouse Tang. The investigators plan to explore to avoid seizures. additional DBS targets to assess whether DBS restored hippocampus-dependent DBS could improve other symptoms of contextual fear and spatial memory in Rett disorder, such as dystonia and poor the Rett model mice to a level similar to coordination. that seen in sham-treated wild-type mice. Hemi Malkki No effect was seen on hippocampus- independent behaviours, such as cue- Original article Hao, S. et al. Forniceal deep brain

NPG dependent fear memory, motor learning stimulation rescues hippocampal memory in Rett syndrome or anxiety. mice. Nature doi:10.1038/nature15694