A cortical map of vestibular representation in the rodent brain revealed by functional imaging and electrophysiology

The vestibular system is important for balance and spatial navigation. It has perhaps more influence on central processing than any other sensory modality, impacting on visual, auditory, motor and even cognitive function. Though several primate studies implicate vestibular modulation of neural activity in visual areas, there is almost nothing known about where and how vestibular information may be integrated at the level of the cortex. As a first step to explore vestibular integration across sensory-motor cortical areas we used electrical stimulation of the vestibular nerve in Lister Hooded rats (~300 g, anesthetized with urethane 1.2 - 1.4 g/kg) together with fMRI and extracellular field and multiunit recordings to establish the first cortical maps of vestibular representation. Electrical stimulation of the VN was confirmed using vestibulo-ocular responses (evoked eye movements). The DC current threshold to elicit this reflex was 296 ± 36 µA (n = 11 rats). Using a train of biphasic pulses at different frequencies, stimulation at 333 Hz had the lowest threshold (206 ± 41 µA, n = 7 rats) and was used for all subsequent experiments. Once VN stimulation was established, rats were placed in a 7T small-animal scanner (Bruker) and the functional connectivity of the VN was mapped with electric stimulation driven fMRI as previously described (Canals et al. 2009 Curr Biol 19:398-403). Functional MRI data were analyzed offline with our own software developed in MATLAB and including the statistical parametric mapping packages (SPM2). After linear detrending, temporal filtering (0.015-0.2 Hz) and spatial filtering (3 x 3 Gaussian kernel of 1.5 sigma) of voxel time series, general linear model analysis was applied with a boxcar convolved with a gamma probability-density function to account for the hemodynamic delay in the BOLD signal. Our results show evoked activity in vestibular brainstem nuclei, vestibular cerebellum, anterior thalamus and multiple higher-order areas, including limbic, motor, and sensory cortices including parietal. In a second group of animals, extracellular recordings using silicone probes from some of the above identified areas such as retrosplenial and somatosensory and motor cortices we identified short latency evoked field potentials and long lasting increases in multiunit firing rates. We therefore suggest that vestibular signaling occurs in several prominent limbic and sensory-motor cortical regions and that the integration of such signals warrants further investigation