Abstract

The use of functional magnetic resonance imaging (fMRI) in mice is increasingly prevalent, providing a means to non-invasively characterise functional abnormalities associated with genetic models of human diseases. The predominant stimulus used in task-based fMRI in the mouse is electrical stimulation of the paw. Task-based fMRI in mice using visual stimuli remains underexplored, despite visual stimuli being common in human fMRI studies. In this study, we map the mouse brain visual system with BOLD measurements at 9.4T using flashing light stimuli with medetomidine anaesthesia. BOLD responses were observed in the lateral geniculate nucleus, the superior colliculus and the primary visual area of the cortex, and were modulated by the flashing frequency, diffuse vs focussed light and stimulus context. Negative BOLD responses were measured in the visual cortex at 10Hz flashing frequency; but turned positive below 5Hz. In addition, the use of interleaved snapshot GE-EPI improved fMRI image quality without diminishing the temporal contrast-noise-ratio. Taken together, this work demonstrates a novel methodological protocol in which the mouse brain visual system can be non-invasively investigated using BOLD fMRI.

Highlights

  • Understanding visual processing is a fundamental objective within neuroscience (Huberman and Niell, 2011) and the use of transgenic mouse models allows genetic influences on vision to be selectively investigated

  • Based on previous functional magnetic resonance imaging (fMRI) experiments conducted in the rat (Bailey et al, 2013; Pawela et al, 2008), we examined the dependence of the blood oxygenation level dependent (BOLD) response on the flashing frequency f of the stimulus

  • Bilateral BOLD responses to a flashing light visual stimulus were identified in the LGd, superior colliculus (SCs) and VISp regions through fixed effects SPM analysis

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Summary

Introduction

Understanding visual processing is a fundamental objective within neuroscience (Huberman and Niell, 2011) and the use of transgenic mouse models allows genetic influences on vision to be selectively investigated. The mouse brain visual system has been extensively studied by electrophysiological recordings (Grubb and Thompson, 2003; Niell and Stryker, 2008; Wang et al, 2010) and multi-photon microscopy (Kerr and Denk, 2008) These techniques provide a more direct measure of neuronal activity in comparison to the blood oxygenation level dependent (BOLD) signal typically measured in functional magnetic resonance imaging (fMRI) studies of human visual pathways. These methods and other optical techniques (Lim et al, 2015; White et al, 2011) require surgery to expose the brain, and can only measure limited sections of the brain at a time. That responses to dark flashes are stronger in visual cortex may suggest that the visual cortex is more closely associated with the interpretation of dark temporal edges, relative to subcortical regions

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