New Technique Helps Uncover Changes in ALS Neurons


Source: Northwestern University

Summary: Researchers have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells.


The excitability changes observed in ALS patient neurons most likely represent the early steps in the disease process. The fact that these changes are detectable in stem cell-derived neurons offers the hope that interventions that affect excitability could affect disease progression before symptoms begin. Researchers from the Northwestern University, in a new study have discovered that some neurons affected by amyotrophic lateral sclerosis (ALS) display hypo-excitability, using a new method to measure electrical activity in cells. This new technique, called optopatch, allows scientists to measure electricity in cells en masse, in contrast to the current method, which forces scientists to measure activity in cells one at a time. The study findings were published in the journal Stem Cell Reports.

ALS motor neurons

ALS patient motor neurons obtained through optopatch recordings. Credit: Northwestern University

In the current study, the team created patient-derived spinal cord motor neurons from ALS patient stem cells and used the optopatch technique to examine the electrical patterns from thousands of neurons the first time the approach has been used to study a human disease model. They found that ALS neurons were hyper-excitable under normal conditions, but became hypo-excited when prompted to fire rapidly. These findings are in line with what previous studies have shown about the transition from hyper-excitability to hypo-excitability and eventually cell death in ALS neurons. In addition, they found only some ALS neurons exhibited these characteristics; the rest appeared normal. In the future, the team hopes to examine whether other genetic sub-types of ALS exhibit these alterations in excitability and search for molecules that can reverse those changes.

Asst. Prof. Evangelos Kiskinis said, “These observations highlight the importance of analyzing neuronal recordings at the single-cell level, rather than simply looking at aggregate population-level statistics,” and further added, “We are intrigued to find what makes some of our cells vulnerable while others are resistant to this phenotype.”


More Information: Evangelos Kiskinis et al, “All-Optical Electrophysiology for High-Throughput Functional Characterization of a Human iPSC-Derived Motor Neuron Model of ALS, Stem Cell Reports (2018). DOI: 10.1016/j.stemcr.2018.04.020


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