Detection of functional connectivity in the resting mouse brain

Fatima A. Nasrallah, Hui-Chien Tay, Kai-Hsiang Chuang

Resting-state functional connectivity, manifested as spontaneous synchronous activity in the brain, has been detected by functional MRI (fMRI) across species such as humans, monkeys, and rats. Yet, most networks, especially the classical bilateral connectivity between hemispheres, have not been reliably found in the mouse brain. This could be due to anesthetic effects on neural activity and difficulty in maintaining proper physiology and neurovascular coupling in anesthetized mouse. For example, α2 adrenoceptor agonist, medetomidine, is a sedative for longitudinal mouse fMRI. However, the higher dosage needed compared to rats may suppress the functional synchrony and lead to unilateral connectivity. In this study, we investigated the influence of medetomidine dosage on neural activation and resting-state networks in mouse brain. We show that mouse can be stabilized with dosage as low as 0.1mg/kg/h. The stimulation-induced somatosensory activation was unchanged when medetomidine was increased from 0.1 to 6 and 10 folds. Especially, robust bilateral connectivity can be observed in the primary, secondary somatosensory and visual cortices, as well as the hippocampus, caudate putamen, and thalamus at low dose of medetomidine. Significant suppression of inter-hemispheric correlation was seen in the thalamus, where the receptor density is high, under 0.6mg/kg/h, and in all regions except the caudate, where the receptor density is low, under 1.0mg/kg/h. Furthermore, in mice whose activation was weaker or took longer time to detect, the bilateral connectivity was lower. This demonstrates that, with proper sedation and conservation of neurovascular coupling, similar bilateral networks like other species can be detected in the mouse brain.