FMRP regulates adult human cortical excitability via cyclic-AMP signalling

Knops, M. J.; Meftah, S.; Wilson, M. A.; Taylor, L. W.; Bonthron, C.; Bilal, A.; Liaquat, I.; Brennan, P. M.; Durrant, C. S.; Booker, S. A.

doi:10.1101/2025.10.14.682273

bioRxiv · 10.1101/2025.10.14.682273

FMRP regulates adult human cortical excitability via cyclic-AMP signalling

Knops, M. J.·Meftah, S.·Wilson, M. A.·Taylor, L. W.·Bonthron, C.·Bilal, A.·Liaquat, I.·Brennan, P. M.·Durrant, C. S.·Booker, S. A.

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Abstract

Fragile X Syndrome (FXS) is a common inherited neurodevelopmental condition, resulting from loss of Fragile X Messenger Ribonuclear Protein (FMRP). Rodent models of FXS display cellular hyperexcitability, but it is not known to what extent this is the case in intact human neurons. Depleting FMRP in human brain slice cultures reveals cyclic-AMP-dependent cellular hyperexcitability which is corrected by phosphodiesterase 4D inhibition and may be independent of neurodevelopment.

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Knops, M. J., Meftah, S., Wilson, M. A., Taylor, L. W., Bonthron, C., Bilal, A., Liaquat, I., Brennan, P. M., Durrant, C. S., Booker, S. A.. 2025-10-14. FMRP regulates adult human cortical excitability via cyclic-AMP signalling. https://doi.org/10.1101/2025.10.14.682273

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