TRPV3 channel activity helps cortical neurons stay active during fever

Fever raises body temperature (Tb) from ~37 °C to beyond 38.4 °C to combat
pathogens. While generally well tolerated below 40 °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°C to 36 °C and 39 °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 °C. Moreover, in Trpv3-/- mice,
temperature increases to 39 °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.