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

National Institute On Alcohol Abuse And Alcoholism

Investigators

Linked publications, trials & patents

Abstract

The renewal of the animal protocol “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 loss of key research personnel in early 2025, we have made significant progress across several areas of study. Specifically, we have: 1. Identified brain networks and mechanisms that contribute to specific types of learning deficits in ASD. 2. Discovered an abnormal form of brain plasticity that may underlie learning deficits associated with in utero environmental insults. 3. Demonstrated that exposure to febrile temperatures alone can alleviate ASD symptoms by dampening activity of specific voltage-gated channels. 4. Shown how components of fever differentially regulate brain activity across distinct cell classes, including pyramidal neurons, medium spiny neurons, and several interneuron subtypes. 5. Uncovered neural circuit mechanisms in the developing cortex that safeguard the brain during fever. 6. Identified brain regions affected by the thermal and immune components of fever, and how these influences may determine which symptoms are alleviated in epilepsy and ASD depending on the underlying genetic variant. At present, we are submitting, revising, or preparing six manuscripts to report these findings. Looking ahead, our work will focus on extending these discoveries across multiple genetic variants associated with heightened susceptibility to ASD and/or epilepsy. Achieving these goals will significantly advance efforts to translate the beneficial effects of fever into novel treatment strategies.