Longitudinal [18]UCB-H/[18F]FDG imaging depicts complex patterns of structural and functional neuroplasticity following bilateral vestibular loss in the rat

Abstract

Neuronal lesions trigger mechanisms of structural and functional neuroplasticity, which can support recovery. However, the temporal and spatial appearance of structure–function changes and their interrelation remain unclear. The current study aimed to directly compare serial whole-brain in vivo measurements of functional plasticity (by [18F]FDG-PET) and structural synaptic plasticity (by [18F]UCB-H-PET) before and after bilateral labyrinthectomy in rats and investigate the effect of locomotor training. Complex structure–function changes were found after bilateral labyrinthectomy: in brainstem-cerebellar circuits, regional cerebral glucose metabolism (rCGM) decreased early, followed by reduced synaptic density. In the thalamus, increased [18F]UCB-H binding preceded a higher rCGM uptake. In frontal-basal ganglia loops, an increase in synaptic density was paralleled by a decrease in rCGM. In the group with locomotor training, thalamic rCGM and [18F]UCB-H binding increased following bilateral labyrinthectomy compared to the no training group. Rats with training had considerably fewer body rotations. In conclusion, combined [18F]FDG/[18F]UCB-H dual tracer imaging reveals that adaptive neuroplasticity after bilateral vestibular loss is not a uniform process but is composed of complex spatial and temporal patterns of structure–function coupling in networks for vestibular, multisensory, and motor control, which can be modulated by early physical training.

Longitudinal Regional Brain Activation and Behavioral Responses to Repetitive Low-Intensity Vestibular Noise Stimulation in a Bilateral Vestibular Loss Rat Model

“…As reported previously [30], chemical BL resulted in an acute decrease of neuronal activity within brainstem-cerebellar networks encompassing primary and secondary processing hubs (e.g., vestibular nuclei, inferior colliculus) of sensory cues from peripheral vestibular and auditory afferents. Decreased regional neuronal activity in brainstem-cerebellar networks only partially recovered during the studied period of 60 days post-BL.…”

“…In all rodents, a chemical BL was performed by transtympanic injection of bupivacaine and parsenic acid. On days 1,3,6,7,15,21,30,45, and 60 post-BL, low-intensity vestibular noise stimulation (nGVS at 0.2mA; N=8 animals) or sham stimulation (nGVS at 0mA; N=9 animals) was administered. Regional brain activation patterns and locomotion performance were assessed before BL and repetitively until day 60 post-BL.…”

“…In contrast, we observed a predominant acute increase of regional brain activation in hemispheric sensory, motor, and limbic networks in response to BL. Specifically, neuronal activity in the thalamus -a prominent hub for multisensory integration and vestibular-motor action [31] further increased during the course of post-BL recovery, which likely reflects processes of adaptive neuroplasticity that facilitate multisensory substitution and recalibration [30].…”

Loss of calcitonin gene-related peptide (αCGRP) and use of a vestibular challenge highlight balance deficiencies in aging mice

“…The thalamus is an integrative center for multisensory inputs (vestibular, motor, and visual) and recent evidence suggests cerebellar projections from all three cerebellar nuclei reach most thalamic nuclei [ 39 ]. The rat thalamus has been shown to experience adaptive plasticity to bilateral labyrinthine loss [ 40 ]. While the cerebellum has the most CGRP binding sites in the brain and CGRP loss may significantly impact cerebellar activity, multisensory compensation mediated by the thalamus may result in recalibrated networks that can explain the modest rotarod improvements in the αCGRP -KO as they age.…”

Vestibular contribution to spatial orientation and navigation

“…In a bilateral chemical labyrinthectomy rat model, hippocampal glucose metabolism decreased on both sides from days 1–60 post lesion [ 24 ▪ ]. In vivo synaptic density imaging depicted no major synaptic loss in the hippocampus during this time period [ 41 ▪ ]. This finding is in accordance to older in vitro studies, which indicated no major synaptic loss in the hippocampus following bilateral vestibular deafferentation, but only a minor change in dendritic structure [ 42 ].…”