Burning wood in a fire pit. Image credit: Engin Akyurt (CC0)
Fever is a symptom of an infection during which the body temperature rises from just below 37 °C (98.6. 6 °F) to above 38 °C (100.4. 4 °F). This extra heat helps the body fight germs. For most children and adults, a higher temperature – which also affects the brain – causes only milder symptoms such as tiredness, body aches, headache or chills. However, in about 1 in 20 to 1 in 50 children aged 6 months to 5 years, a fever can trigger a seizure. Seizures happen when brain cells, called neurons, become overly active at the same time.
Most studies in rodents have focused on why brain cells become overactive at very high temperatures, around 41 to 42 °C. Much less is known about why seizures are relatively rare at lower temperatures of about 38 to 39 °C. To address this gap, Shen et al. studied how neurons maintain a normal activity at lower temperatures.
The researchers recorded neurons in the somatosensory cortex of mice as their body temperature increased from 30 °C to between 36 °C and 39 °C (fever-range). In young mouse brains, fever induced two simultaneous changes in brain cells: some neurons reduced their activity, allowing them to rest, while others increased their activity to compensate. Because the number of active and less active neurons was roughly balanced, the cells could keep their overall activity stable during a fever.
Moreover, the researchers also identified a thermosensitive protein known as TRPV3 that enhanced its activity during fever. This allowed a sustained flow of ions into the neurons, helping active neurons to keep their firing rate. Rather than increasing seizure risk, this mechanism appears to stabilize neural circuits and prevent excessive synchronization of neurons when fever reduces or pauses activity in many neurons. In addition, active neurons were distinct in that they received greater excitatory input from neighboring neurons and underwent functional adaptations, such as maintaining ion channel expression and distribution, to help preserve effective communication and network stability during fever.
Genetically modified mice lacking TRPV3 showed reduced neuronal activity and a delayed onset of seizures, indicating that TRPV3 is essential in maintaining cortical activity during fever. These findings differ from experiments conducted at very high temperatures, where neuronal overexcitation is driven by breakdowns in ion channel function and inhibitory signaling.
Shen et al. uncovered previously unknown neuronal processes that help the brain continue functioning during fever. This work lays the groundwork for future studies into the causes of fever-related seizures, including whether such seizures arise when compensatory mechanisms fail or when key proteins necessary for maintaining neural balance are overexpressed during elevated body temperatures.
