Enhanced Sensitivity and Altered EEG Patterns During General Anesthesia in BTBR Mice, a Model of Autism

Background/Objectives: Alterations in excitation/inhibition (E/I) balance, involving both inhibitory and excitatory signaling, have been implicated in the pathophysiology of autism spectrum disorder (ASD). Volatile anesthetics, including sevoflurane, act on multiple molecular and network targets, and anesthetic sensitivity may therefore differ in ASD. This study investigated whether sevoflurane sensitivity is altered in BTBR T+Itpr3tf/J (BTBR) mice, a widely used mouse model of ASD. Methods: Sevoflurane sensitivity was compared between BTBR mice and C57BL/6J (B6) control mice using behavioral and electroencephalographic (EEG) analyses. The minimum alveolar concentration required to abolish nociceptive responses (MACsevo) and the sevoflurane concentration associated with recovery of the righting reflex (RRsevo) were measured. Dose-dependent EEG changes, including burst suppression and theta power distribution, were also evaluated. Results: MACsevo did not differ significantly between BTBR and B6 mice. However, RRsevo was significantly lower in BTBR mice (1.10 ± 0.10%) compared with B6 mice (1.65 ± 0.13%; p < 0.001). EEG analyses demonstrated that burst suppression occurred at lower sevoflurane concentrations in BTBR mice (2.0%) than in B6 mice (2.4%). In addition, topographical mapping revealed distinct theta power dynamics between the two strains during anesthesia. Conclusions: BTBR mice exhibit increased sensitivity to sevoflurane during emergence from anesthesia and show distinct EEG patterns compared with control mice. These findings suggest altered anesthetic responsiveness in a mouse model of ASD and support the possibility that network-level neurophysiological differences may influence anesthetic responses. Further studies are needed to clarify whether similar alterations are present across other ASD models and human ASD populations.