Cortical neurons derived from human pluripotent stem cells lacking FMRP display altered spontaneous firing patterns.
Shreya Das Sharma, Rakhi Pal, Bharath Kumar Reddy and 13 others
PMID 32560741WHAT IT FOUND
Neurons grown from fragile X stem cell lines fired in bursts more often and for shorter periods than control neurons.
Their basic excitability and synaptic activity were unchanged.
Key findings
01Neurons lacking FMRP fired spontaneous bursts more often and for shorter periods than neurons with FMRP.
02No differences were found in passive or active membrane properties, or in miniature excitatory postsynaptic current frequency and amplitude, between FMRP-lacking and control neurons.
03In the lines tested, persistent sodium current and calcium-activated potassium current densities were lower in FMRP-lacking lines than in control lines.
STILL TO COME
How it was doneWhat they found
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What it does not show
The work was done in lab-grown human cortical neurons, not in patients, so it does not show how a person with fragile X syndrome functions in daily life. The cultures contained mainly glutamatergic neurons and no GABAergic interneurons, so the recorded network activity may not match intact human cortex. The neurons had membrane properties consistent with developmental immaturity, so adult cortical activity may differ. The paper did not test any therapy or clinical outcome.
Declared interests
Funding was named from the Department of Biotechnology, Government of India; Simons Foundation Autism Research Initiative; Patrick Wild Centre; National Institutes of Health; Cedars-Sinai Programmatic Funds; and David and Janet Polak Foundation. No competing interest declaration is given in the supplied text.
The easy way to misread this
Do not read these lab findings as evidence that any treatment changes fragile X symptoms in patients. The study used stem cell-derived neurons in vitro and did not test clinical outcomes.