Fever-like body heat reduces cognitive differences in preclinical autism model

Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by differences in communication, social interactions, learning and sensory processing. Research has shown that some autistic children experience temporary improvements in communication, hyperactivity, repetitive behaviors, and mental functions when they have a fever, a phenomenon known as the "fever effect." However, the underlying mechanisms of this effect have remained unclear.

A team of researchers at the National Institutes of Health conducted a study using a mouse model of autism to investigate the processes driving the fever effect. Their findings, published in Molecular Psychiatry, indicate that the heat associated with a fever, rather than the immune activation causing it, may alter neuron firing and trigger cognitive changes.

The study focused on behavioral measures of learning and sensory-cognitive function, particularly tactile (touch) processing, as sensory abnormalities are common in autism.

The researchers performed experiments with Scn2a+/- juvenile mice, which exhibit autism-like behaviors due to carrying only one functional copy of the Scn2a gene. When these mice were exposed to a fever-like temperature, they were able to locate the correct escape hole in a maze much faster than at normal body temperature, indicating improved problem-solving, learning, and spatial navigation abilities.

The researchers also found that tactile-seeking behaviors, such as frequently touching textured objects or interacting excessively with familiar objects, improved following exposure to fever-like temperatures.

To unravel the neural processes behind these improvements, the researchers recorded brain activity in the mice's somatosensory cortex, a region involved in processing tactile information. At normal body temperature, neurons in this region showed abnormal increased spiking activity. However, when the temperature was raised to fever levels, the activity normalized.

The team observed that at fever-like temperatures, the spike threshold (the voltage at which a neuron becomes active) of these neurons increased, with a greater increase in neurons that became inactive compared to those that remained active.

Further investigation revealed that potassium channels in the brain contribute to the suppression of excess neuronal firing during fever-like temperatures. Lower temperatures reduced potassium currents, while increasing temperatures led to larger potassium currents. Introducing a potassium-channel blocker prevented the temperature-induced increase in spike threshold, providing evidence that potassium channels play a role in the fever effect.

Finally, the researchers attempted to replicate the beneficial effects of fever using pharmacological compounds and genetic techniques. Treating the mice with drugs that enhanced potassium-channel activity and using genetically engineered receptors to control selected neurons both improved tactile discrimination, suggesting that reducing neuronal activity could partially mimic the positive effects of fever-like temperatures.