Deciphering the mechanisms mediating the dichotomous effects of fever on brain function and behavior

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The renewal of the animal protocol for "Deciphering the mechanisms mediating the dichotomous effects of fever on brain function and behavior" was approved by the Animal Care and Use Committee on 07/29/2023. Despite the challenges posed by the COVID-19 pandemic, which impacted research progress in 2020 and 2021, we have made significant strides in various study areas. Specifically, we have: 1. Identified brain networks and mechanisms that contribute to certain types of learning deficits in individuals with ASD (Autism Spectrum Disorder). 2. Demonstrated that exposure to febrile temperatures alone can effectively alleviate ASD symptoms, owing to unique effects that dampen activity in specific voltage-gated channels. 3. Shown that fever can modulate overall activity levels in the cortex. 4. Uncovered neural circuit mechanisms that are specifically activated in the developing cortex to safeguard the brain during fever. At present, we are in the process of revising or preparing manuscripts to report these significant findings. Our future endeavors will involve extending the applicability of our findings to encompass four primary genetic variants associated with heightened susceptibility to ASD. Additionally, we will validate our discoveries within a recently established environmental-induced ASD model. The successful achievement of these objectives will significantly advance our efforts to enable the targeted use of pharmacological agents that induce fever-like temperatures as a treatment approach for ASD symptoms.