Mechanistic Insight into Angelman Syndrome Treatments
Luis O. Romero, Manisha Bade, Elisa Carrillo, Sonia Paz-López, Syed A. M. Hasan et al.
(see article e0965252025)
People with Angelman syndrome (AS) experience impaired motor coordination and cognition. Previous studies probing mechanisms of these symptoms implicate reduced filamentous actin in dorsal root ganglia (DRG) and hippocampal neurons, as well as altered activity of a mechanosensitive ion channel (PIEZO2) and a glutamate receptor (AMPA). In this issue, Romero and colleagues explored links between these observations and whether preventing this reduction in filamentous actin can improve symptoms. To reverse the actin mechanism, the researchers targeted an actin-binding protein called cofilin with a selective pharmacological inhibitor (SZ-3) in an AS mouse model. SZ-3 restored PIEZO2 and AMPA activity, promoted neuronal excitability, and improved motor coordination and learning in the AS mice. According to the researchers, these findings suggest that targeting cofilin may alleviate some of the symptoms of AS.
Micrographs of mouse DRG neurons (top) transfected with cofilin siRNA and a transfection marker in green (bottom). The micrographs represent at least 10 independent preparations. Black and white arrows show a transfected neuron. See Romero et al. for more information.
Aperiodic—Not Oscillatory—Activity May Represent Connectivity
Noemie Monchy, Joan Duprez, Jean-François Houvenaghel, Alexandre Legros, Bradley Voytek, and Julien Modolo
(see article e1041252025)
In studies that use electroencephalography and magnetoencephalography, researchers typically identify functional neural networks by looking for oscillatory brain activity. In this issue, Monchy et al. find evidence contradicting the assumption that oscillatory activity represents coupled brain regions. Using multiple human datasets during resting state and a cognitive task, the authors found that aperiodic activity more closely represents three different brain networks (delta, theta, and gamma) than oscillatory activity. Furthermore, oscillatory activity may be more sparse than previous work suggests. According to Monchy and colleagues, this study is among the first to quantify the contributions of aperiodic activity on functional brain networks. The authors suggest that this work may improve the reproducibility of functional connectivity research in cognitive and clinical neuroscience fields.
Footnotes
This Week in The Journal was written by Paige McKeon
