Optogenetic fMRI interrogation of brain-wide central vestibular pathways

Abstract

Blood oxygen level-dependent functional MRI (fMRI) constitutes a powerful neuroimaging technology to map brain-wide functions in response to specific sensory or cognitive tasks. However, fMRI mapping of the vestibular system, which is pivotal for our sense of balance, poses significant challenges. Physical constraints limit a subject’s ability to perform motion- and balance-related tasks inside the scanner, and current stimulation techniques within the scanner are nonspecific to delineate complex vestibular nucleus (VN) pathways. Using fMRI, we examined brain-wide neural activity patterns elicited by optogenetically stimulating excitatory neurons of a major vestibular nucleus, the ipsilateral medial VN (MVN). We demonstrated robust optogenetically evoked fMRI activations bilaterally at sensorimotor cortices and their associated thalamic nuclei (auditory, visual, somatosensory, and motor), high-order cortices (cingulate, retrosplenial, temporal association, and parietal), and hippocampal formations (dentate gyrus, entorhinal cortex, and subiculum). We then examined the modulatory effects of the vestibular system on sensory processing using auditory and visual stimulation in combination with optogenetic excitation of the MVN. We found enhanced responses to sound in the auditory cortex, thalamus, and inferior colliculus ipsilateral to the stimulated MVN. In the visual pathway, we observed enhanced responses to visual stimuli in the ipsilateral visual cortex, thalamus, and contralateral superior colliculus. Taken together, our imaging findings reveal multiple brain-wide central vestibular pathways. We demonstrate large-scale modulatory effects of the vestibular system on sensory processing.

Vestibular function and cortical and sub-cortical alterations in an aging population

“…Most of the significant regions in the hippocampus were in CA1, followed by CA2. This is consistent with animal studies that have shown evoked field potentials, increased single neuron discharge, increased activation using fMRI, and c-Fos activation – all in CA1 – following electrical activation of the peripheral vestibular system [ 6 , 12 , 63 , 69 , 70 ]. Moreover, several studies have shown that vestibular lesions result in loss of location-specific firing of place cells, which largely reside in CA1 [ 71 , 72 ].…”

“…However, the exact pathways through which the loss of vestibular function may affect cognition is unknown. Functional neuroimaging studies in healthy subjects have shown that vestibular stimulation activates a large multisensory cortical and subcortical network, which primarily includes the insula, temporo-parietal junction, somatosensory cortex, hippocampus, medial entorhinal cortex (ERC), several thalamic nuclei, and basal ganglia [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. One prior study found that poorer vestibular function in older adults was associated with significantly reduced hippocampal volumes [ 18 ].…”

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion

“…Diminished metabolism was found in ipsilateral entorhinal, visual, and somatosensory cortical areas. This is in line with the concept of a reciprocal inhibitory interaction between the sensory systems, i.e., activation of the vestibular system by GVS and downregulation of the visual and somatosensory systems (52), and was recently supported by imaging data on multiple central vestibular pathways that exert "large-scale modulatory effects of the vestibular system on sensory processing" (53).…”

The Impact of Optogenetics on Regenerative Medicine

“…This strategy allowed an optogenetic stimulation, followed by an electrophysiological response of PNS [41]. The vestibular system is controlled by neurons within the vestibular nucleus (VN), stimulating the auditory, visual, and motor centers [42]. Generally, through fMRI (functional magnetic resonance), brain functions are mapped in response to different sensory or cognitive tasks; however, fMRI does not work well in the studies on VN.…”