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bioRxiv · 10.1101/2024.09.09.612112

TRPV3 channel activity helps cortical neurons stay active during fever

Shen, Y.·Fiath, R.·Ulbert, I.·Antoine, M.
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Abstract

Fever raises body temperature (Tb) from [~]37 {degrees}C to beyond 38.4 {degrees}C to combat pathogens. While generally well tolerated below 40 {degrees}C, in rare cases fever can abnormally elevate neural activity and induce seizures in neurotypical children aged 2-5 years. This study investigates the mechanisms by which neuronal activity is maintained and stabilized during exposure to fever-range temperatures. Recordings of layer (L)4-evoked spiking in L2/3 pyramidal neurons (PNs) of mouse somatosensory cortex revealed four outcomes as temperature increased from 30{degrees}C to 36 {degrees}C and 39 {degrees}C (fever-range): neurons remained inactive, stayed active, ceased activity, or initiated activity. Roughly equal proportions of neurons ceased or initiated spiking, making the subset of "STAY" PNs, those that remain active across temperatures, crucial for maintaining stable cortical output. STAY PNs were more prevalent at younger postnatal ages. Their firing stability was supported by a distinct ion channel composition, including the thermosensitive channel TRPV3, which enables continued spiking by adjusting depolarization to meet spike threshold. Intracellular blockade of TRPV3, but not TRPV4, significantly reduced the proportion of STAY PNs and suppressed spiking at 39 {degrees}C. Moreover, in Trpv3-/-mice, temperature increases to 39 {degrees}C reduced both spiking and postsynaptic potential amplitude, and these mice exhibited a delayed seizure onset. Together, these findings suggest that TRPV3 contributes to the preservation of cortical activity during fever.

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Shen, Y., Fiath, R., Ulbert, I., Antoine, M.. 2024-09-16. TRPV3 channel activity helps cortical neurons stay active during fever. https://doi.org/10.1101/2024.09.09.612112

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