Core body temperature is regulated to a setpoint between 36.1 to 37.8°C, with an average fluctuation of 0.5°C during a 24-hour day. Despite mechanistic safeguards, major temperature deviations (1-3°C) from the setpoint occur in the body and in turn the brain. For unknown reasons, in most mammals (humans included), these increases in brain temperature are benign. However, macro-fluctuations in brain temperature in some cases result in deleterious outcomes such as seizures. In this talk, I will describe a mechanism for circuit-level adaptive regulation of cortical activity during macro-fluctuations in brain temperature. I will also discuss how this mechanism can be applied towards the understanding of the pathology of Autism Spectrum Disorder.