Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion

Abstract

The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM at each PLD compared to pre-lesion status were performed. After lesion, augmented metabolic activation by GVS was detected in cerebellum, mainly contralateral, and in contralateral subcortical structures such as superior colliculus, while diminished activation was observed in ipsilateral visual, entorhinal, and somatosensory cortices, indicating compensatory processes in the non-affected sensory systems of the unlesioned side. The changes in rCGM observed after lesion resembled alterations observed in patients suffering from unilateral thalamic infarction and may be interpreted as brain plasticity mechanisms associated with vestibular compensation and substitution. The second set of experiments aimed at the connections between cortical and subcortical vestibular regions and their neurotransmitter systems. Neuronal tracers were injected in regions processing vestibular and somatosensory information. Injections into the anterior cingulate cortex (ACC) or the primary somatosensory cortex (S1) retrogradely labeled neuronal somata in ventral posteromedial (VPM), posterolateral (VPL), ventrolateral (VL), posterior (Po), and laterodorsal nucleus, dorsomedial part (LDDM), locus coeruleus, and contralateral S1 area. Injections into the parafascicular nucleus (PaF), VPM/VPL, or LDDM anterogradely labeled terminal fields in S1, ACC, insular cortex, hippocampal CA1 region, and amygdala. Immunohistochemistry showed tracer-labeled terminal fields contacting cortical neurons expressing the µ-opioid receptor. Antibodies to tyrosine hydroxylase, serotonin, substance P, or neuronal nitric oxide-synthase did not label any of the traced structures. These findings provide evidence for opioidergic transmission in thalamo-cortical transduction.

Activation of the VpdmVGLUT1-VPM pathway contributes to anxiety-like behaviors induced by malocclusion

“…We focused on an ascending pathway, namely, the trigeminal-thalamic-cortex pathway, which might relay orofacial information from trigeminal nuclei to the cortex. The VPM is the main target of the Vpdm ( Smith, 1975 ; Ge et al, 2010 ; Andrew et al, 2020 ) and connects reciprocally with the SI ( Oda et al, 2004 ; Kropf et al, 2019 ; Reuss et al, 2020 ). Previous reports have demonstrated that the Vpdm-VPM and VPM-SI pathways both participate in the modulation of proprioceptive disorders and negative emotion ( Capra et al, 1994 ; Ge et al, 2010 ; Sato et al, 2017 ; Yoshida et al, 2017 ; Tsutsumi et al, 2018 ).…”

“…Dysfunction of the thalamocortical pathway is associated with proprioceptive disorders ( Sato et al, 2017 ; Tsutsumi et al, 2018 ) and negative emotions ( Ramsay, 2019 ; Sheffield et al, 2020 ; Wei et al, 2020 ). The SI, a well-known brain region that participates in emotional regulation ( Kropf et al, 2019 ; Jin et al, 2020 ), is connected reciprocally with the VPM ( Oda et al, 2004 ; Kropf et al, 2019 ; Reuss et al, 2020 ). In inflammatory pain-induced comorbid anxiety, enhanced excitation of the SI-dorsolateral striatum pathway has been observed ( Jin et al, 2020 ).…”

The Differential Effects of Acute Right- vs. Left-Sided Vestibular Deafferentation on Spatial Cognition in Unilateral Labyrinthectomized Mice

“…This lateralization of vestibular information processing was observed in ontogenetic older species. Vestibular processing in rodents was reported to be dominated by the left hemisphere regardless of handedness ( 41 , 42 ). In rodents, the left-sided vestibular information is processed by more complex cortical and subcortical networks than the processing of information from the right-sided vestibular input ( 41 ).…”