Differential effects of anesthetics on resting state functional connectivity in the mouse

Blood oxygen level-dependent (BOLD) functional MRI (fMRI) is a standard approach to examine resting state functional connectivity (RSFC), but fMRI in animal models is challenging. Recently, functional optical intrinsic signal imaging-which relies on the same hemodynamic signal underlying BOLD fMRI-has been developed as a complementary approach to assess RSFC in mice. Since it is difficult to ensure that an animal is in a truly resting state while awake, RSFC measurements under anesthesia remain an important approach. Therefore, we systematically examined measures of RSFC using non-invasive, widefield optical intrinsic signal imaging under five different anesthetics in male C57BL/6J mice. We find excellent seed-based, global, and interhemispheric connectivity using tribromoethanol (Avertin) and ketamine-xylazine, comparable to results in the literature including awake animals. Urethane anesthesia yielded intermediate results, while chloral hydrate and isoflurane were both associated with poor RSFC. Furthermore, we found a correspondence between the strength of RSFC and the power of low-frequency hemodynamic fluctuations. In conclusion, Avertin and ketamine-xylazine provide robust and reproducible measures of RSFC in mice, whereas chloral hydrate and isoflurane do not.R25 NS065743 - NINDS NIH HHS; KL2 TR002542 - NCATS NIH HHS; R00 AG042026 - NIA NIH HHS; K08 NS112601 - NINDS NIH HHS; P01 NS055104 - NINDS NIH HHS; R01 MH111359 - NIMH NIH HHS; R01 NS102969 - NINDS NIH HHS; R01 AA027097 - NIAAA NIH HHS; R01 NS091230 - NINDS NIH HHSPublished versio