Galvanic Vestibular Stimulation Improves Spatial Cognition After Unilateral Labyrinthectomy in Mice

Abstract

Objectives: To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL).Methods: Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0–4 via the electrodes inserted subcutaneously close to both bony labyrinths.Results: Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p < 0.001) and 7 (p < 0.05, Kruskal–Wallis and Mann–Whitney U tests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p < 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p < 0.01).Conclusions: UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.

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

“…Both the Lt.-UL and Rt.-UL groups underwent UL, which was carried out according to a surgery protocol as previously described ( 22 , 45 – 49 ). The mice from the control group underwent sham surgery to expose the semicircular canal (SCC) without labyrinthectomy.…”

“…To apply GVS, we implanted a button-type electrode near the bony labyrinths and connected it to a direct current (DC) shifted galvanic stimulator (A-M Systems Model 2200 Analog Stimulus Isolator) via a wire with an insulated section that passed through the skin, as previously described ( 22 ). A subthreshold, bipolar, sinusoidal GVS current of 0.1 mA and 1 Hz was generated by a computer-controlled stimulator and delivered over a 30-min session, once a day for 5 days.…”

“…The mice were acclimatized to laboratory conditions for 1 week before the experiment started, housed separately, and kept in a controlled temperature and humidity room with free access to food and water. Both the Lt.-UL and Rt.-UL groups underwent UL, which was carried out according to a surgery protocol as previously described (22,(45)(46)(47)(48)(49). The mice from the control group underwent sham surgery to expose the semicircular canal (SCC) without labyrinthectomy.…”

“…BVL results in bilateral hippocampus atrophy, which is associated with spatial memory deficits (17). Though to a lesser extent, unilateral vestibular deafferentation (UVD) has been shown to also impair spatial cognition (18)(19)(20)(21)(22). In addition, UVD in rodents has been revealed to lead to long-term changes in the neurochemical and electrophysiological properties of the hippocampus that contribute to spatial cognitive impairments (23)(24)(25).…”

“…Galvanic vestibular stimulation (GVS) exhibits beneficial effects on spatial memory and navigation tasks by modulating the regularity of the firing rate of vestibular afferents (26)(27)(28). Further, improvement might in part be due to frequent activation of the vestibular hair cells and the neurons in the vestibular nuclei as well as the hippocampus (22,29).…”