The Effects of Complete Vestibular Deafferentation on Spatial Memory and the Hippocampus in the Rat: The Dunedin Experience

in Multisensory Research
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Our studies conducted over the last 14 years have demonstrated that a complete bilateral vestibular deafferentation (BVD) in rats results in spatial memory deficits in a variety of behavioural tasks, such as the radial arm maze, the foraging task and the spatial T maze, as well as deficits in other tasks such as the five-choice serial reaction time task (5-CSRT task) and object recognition memory task. These deficits persist long after the BVD, and are not simply attributable to ataxia, anxiety, hearing loss or hyperactivity. In tasks such as the foraging task, the spatial memory deficits are evident in darkness when vision is not required to perform the task. The deficits in the radial arm maze, the foraging task and the spatial T maze, in particular, suggest hippocampal dysfunction following BVD, and this is supported by the finding that both hippocampal place cells and theta rhythm are dysfunctional in BVD rats. Now that it is clear that the hippocampus is adversely affected by BVD, the next challenge is to determine what vestibular information is transmitted to it and how that information is used by the hippocampus and the other brain structures with which it interacts.

The Effects of Complete Vestibular Deafferentation on Spatial Memory and the Hippocampus in the Rat: The Dunedin Experience

in Multisensory Research

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References

BaekJ.-H.ZhengY.DarlingtonC. L.SmithP. F. (2010). Evidence that spatial memory deficits in rats following bilateral vestibular loss is probably permanentNeurobiol. Learn. Mem. 94402413.

BesnardS.MachadoM. L.VignauxG.BoulouardM.CoquerelA.BouetV.FreretT.DeniseP.Lelong-BoulouardV. (2012). Influence of vestibular input on spatial and nonspatial memory and on hippocampal NMDA receptorsHippocampus 22814826.

BrandtT.SchautzerF.HamiltonD. A.BruningR.MarkowitschH.KallaR.DarlingtonC. L.SmithP. F.StruppM. (2005). Vestibular loss causes hippocampal atrophy and impaired spatial memory in humansBrain 12827322741.

ChapuisN.KrimmM.de WaeleC.VibertN.BerthozA. (1992). Effect of post-training unilateral labyrinthectomy in a spatial orientation task by guinea pigsBehav. Brain Res. 51115126.

CurthoysI. S.HalmagyiG. M. (1995). Vestibular compensation: a review of the ocular motor, neural and clinical consequences of unilateral vestibular lossJ. Vest. Res. 567107.

CutfieldN. J.ScottG.WaldmanA. D.SharpD. J.BronsteinA. M. (2014). Visual and proprioceptive interaction in patients with bilateral vestibular lossNeuroimage Clin. 4274282.

CuthbertP. C.GilchristD. P.HicksS. L.MacDougallH. G.CurthoysI. S. (2000). Electrophysiological evidence for vestibular activation of the guinea pig hippocampusNeuroReport 1114431447.

GobleT. J.MøllerA. R.ThompsonL. T. (2009). Acute high-intensity sound exposure alters responses of place cells in hippocampusHear. Res. 2535259.

GoddardM.ZhengY.DarlingtonC. L.SmithP. F. (2008a). Locomotor and exploratory behaviour in the rat following bilateral vestibular deafferentationBehav. Neurosci. 122448459.

GoddardM.ZhengY.DarlingtonC. L.SmithP. F. (2008b). Synaptic protein expression in the medial temporal lobe and frontal cortex following chronic bilateral vestibular lossHippocampus 18440444.

GoddardM.ZhengY.DarlingtonC. L.SmithP. F. (2008c). Monoamine transporter and enzyme expression in the medial temporal lobe and frontal lobes following chronic bilateral vestibular lossNeurosci. Lett. 437107110.

HitierM.BesnardS.SmithP. F. (2014). Vestibular pathways involved in cognitionFront. Integr. Neurosci. 859116.

HoriiA.TakedaN.MochizukiT.Okakura-MochizukiK.YamamotoY.YamatodaniA. (1994). Effects of vestibular stimulation on acetylcholine release from rat hippocampus: an in vivo microdialysis studyJ. Neurophysiol. 72605611.

HoriiA.RussellN.SmithP. F.DarlingtonC. L.BilkeyD. K. (2004). Vestibular influences on CA1 neurons in the rat hippocampus: an electrophysiological study in vivoExp. Brain Res. 155245250.

HornK. M.DeWittJ. R.NielsonH. C. (1981). Behavioral assessment of sodium arsanilate induced vestibular dysfunction in ratsPhysiol. Psychol. 9371378.

JacobP. Y.PoucetB.LibergeM.SaveE.SargoliniF. (2014). Vestibular control of entorhinal cortex activity in spatial navigationFront Integr. Neurosci. 838.

JeewajeeA.BarryC.O’KeefeJ.BurgessN. (2008). Grid cells and theta as oscillatory interference: electrophysiological data from freely moving ratsHippocampus 1811751185.

LeverC.JeewajeeA.BurtonS.O’KeefeJ.BurgessN. (2009). Hippocampal theta frequency, novelty and behaviorHippocampus 19409410.

LopezC.BlankeO. (2011). The thalamocortical vestibular system in animals and humansBrain Res. Rev. 67119146.

MachadoM. L.Lelong-BoulouardV.SmithP. F.FreretT.PhiloxeneB.DeniseP.BesnardS. (2012). Influence of anxiety in spatial memory impairments related to the loss of vestibular function in ratNeuroscience 218161169.

NeoP.CarterD.ZhengY.SmithP. F.DarlingtonC. L.McNaughtonN. (2012). Septal elicitation of hippocampal theta rhythm did not repair the cognitive and emotional deficits resulting from vestibular lesionsHippocampus 2211761187.

OssenkoppK. P.HargreavesE. L. (1993). Spatial learning in an enclosed eight-arm maze in rats with sodium arsinilate-induced labyrinthectomiesBehav. Neur. Biol. 59253257.

RussellN.HoriiA.SmithP. F.DarlingtonC. L.BilkeyD. (2003a). Effects of bilateral vestibular deafferentation on radial arm maze performanceJ. Vestib. Res. 13916.

RussellN.HoriiA.SmithP. F.DarlingtonC. L.BilkeyD. (2003b). The long-term effects of permanent vestibular lesions on hippocampal spatial firingJ. Neurosci. 2364906498.

RussellN.HoriiA.SmithP. F.DarlingtonC. L.BilkeyD. (2006). Lesions of the vestibular system disrupt hippocampal theta rhythm in the ratJ. Neurophysiol. 96414.

SchaeppiU.KrinkeG.FitzGeraldR. E.ClassenW. (1991). Impaired tunnel-maze behavior in rats with sensory lesions: vestibular and auditory systemsNeurotoxicology 12445454.

ShinderM. E.TaubeJ. S. (2010). Differentiating ascending vestibular pathways to the cortex involved in spatial cognitionJ. Vestib. Res. 20323.

SmithP. F.ZhengY. (2013a). From ear to uncertainty: vestibular contributions to cognitive functionFront. Integr. Neurosci. 784.

SmithP. F.ZhengY. (2013b). Principal component analysis suggests subtle changes in glutamate receptor subunit expression in the rat hippocampus following bilateral vestibular deafferentation in the ratNeurosci. Lett. 548265268.

SmithP. F.HaslettS. J.ZhengY. (2013). A multivariate statistical and data mining analysis of spatial memory-related behavior following bilateral vestibular deafferentation in the ratBehav. Brain Res. 2461523.

StackmanR. W.ClarkA. S.TaubeJ. S. (2002). Hippocampal spatial representations require vestibular inputHippocampus 12291303.

StackmanR. W.HerbertA. M. (2002). Rats with lesions of the vestibular system require a visual landmark for spatial navigationBehav. Brain Res. 1282740.

StilesL.ZhengY.DarlingtonC. L.SmithP. F. (2012). The D2 dopamine receptor and locomotor hyperactivity following bilateral vestibular deafferentation in the ratBehav. Brain Res. 227150158.

TaiS. K.MaJ.OssenkoppK. P.LeungL. S. (2012). Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulationHippocampus 22914925.

WallaceD. G.HinesD. J.PellisS. M.WhishawI. Q. (2002). Vestibular information is required for dead reckoning in the ratJ. Neurosci. 151000910017.

ZhengY.KerrD. S.DarlingtonC. L.SmithP. F. (2003). Peripheral vestibular damage causes a lasting decrease in the electrical excitability of CA1 in hippocampal slices in vitroHippocampus 13873878.

ZhengY.DarlingtonC. L.SmithP. F. (2004). Bilateral vestibular deafferentation impairs object recognition in ratNeuroReport 1519131916.

ZhengY.GoddardM.DarlingtonC. L.SmithP. F. (2007). Bilateral vestibular deafferentation impairs performance in a spatial forced alternation task in ratsHippocampus 17253256.

ZhengY.GoddardM.DarlingtonC. L.SmithP. F. (2009a). Long-term deficits on a foraging task after bilateral vestibular deafferentation in ratsHippocampus 19480486.

ZhengY.BalabhadrapatruniS.MunnO.MasumuraC.DarlingtonC. L.SmithP. F. (2009b). Evidence for deficits in a 5 choice serial reaction time task in rats with bilateral vestibular deafferentationBehav. Brain Res. 203113117.

ZhengY.Mason-ParkerS. E.LoganB.DarlingtonC. L.SmithP. F.AbrahamW. C. (2010). Hippocampal synaptic transmission and LTP in vivo are intact following bilateral vestibular deafferentation in the ratHippocampus 20461468.

ZhengY.HamiltonE.BegumS.SmithP. F.DarlingtonC. L. (2011). The effects of acoustic trauma that can cause tinnitus on spatial performance in ratsNeuroscience 1864856.

ZhengY.CheungI.SmithP. F. (2012a). Performance in anxiety and spatial memory tests following bilateral vestibular loss in the rat and effects of anxiolytic and anxiogenic drugsBehav. Brain Res. 2352129.

ZhengY.BalabhadrapatruniS.ChungP.GliddonC. M.ZhangM.NapperR.BaekJ.-H.BrandtT.StruppM.DarlingtonC. L.SmithP. F. (2012b). The effects of bilateral vestibular loss on hippocampal volume, neuronal number and cell proliferation in ratsFront. Neuro-Otol. 320.

ZhengY.WilsonG.StilesL.SmithP. F. (2013). Glutamate receptor subunit and calmodulin kinase II expression in the rat hippocampus, with and without T maze experience, following bilateral vestibular deafferentationPLoS One 8(2) e54527. DOI:10.1371/journal.pone.0054527.

ZhengY.GeddesL.SatoG.StilesL.DarlingtonC. L.SmithP. F. (2014). Galvanic vestibular stimulation impairs cell proliferation and neurogenesis in the rat hippocampus but not spatial memoryHippocampus 24541552.

zu EulenburgP.StoeterP.DieterichM. (2010). Voxel-based morphometry depicts central compensation after vestibular neuritisAnnal. Neurol. 68241249.

Figures

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    The first and second home choices on the first and the last dark sessions. The big circle represents the foraging table and the eight medium-sized circles equally distributed on the periphery of the table represent the potential home bases. The closed circle represents the old home location, and the striped circle represents the novel home location on the probe trial. The small circle outside the table represents individual sham (open circle) or BVD (closed circle) rats’ first or second home choices. The direction and the length of the arrow in the middle of the table represent the mean direction and tendency of the first or second home choices for sham (open arrow) and BVD (closed arrow) rats. Reproduced with permission from Zheng et al. (2009a).

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    Number of errors (A) and heading angles (B) for the sham and BVD rats during the dark sessions. Data reflect a block of two sessions and are presented as mean ± SEM. Reproduced with permission from Zheng et al. (2009a).

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    Percentage of correct choices in the T maze task for bilateral vestibular deafferentation (BVD) and sham surgery control animals at three weeks (A), three months (B), and five months (C) post-op. Symbols represent means and bars one SE of the mean. Reproduced with permission from Zheng et al. (2007).

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    The mean number of visits to the old home for sham-vehicle, sham-WIN, BVD-vehicle, and BVD-WIN animals in the light probe trial. The data are represented as means. Reproduced with permission from Baek et al. (2010).

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    The frequency of the different initial heading angles for the sham and BVD animals for the dark training. Note that while the angles for the sham animals cluster around 0 and 360 degrees of the circle representing the correct home location on the circular foraging table, the BVD animals are distributed around 360 degrees, indicating that they have no clear sense of direction. Reproduced with permission from Baek et al. (2010).

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    The mean area under the curve (AUC) for the number of errors for the sham and BVD animals to show the effect of surgery and drug treatment during the dark training. Data are represented as mean ± 95% confidence interval. Reproduced with permission from Baek et al. (2010).

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    Scatter graph illustrating the simple regression analysis performed to predict the AUC values for the number of errors made by the sham or BVD animals from the AUCs for their searching velocities. The AUC values were used to perform the regression analysis. Note that there is no relationship between the errors and the searching velocities, as an index of the animals’ hyperactivity. Reproduced with permission from Baek et al. (2010).

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    Mean % correct responses in the spatial T maze task for the BVD and sham animals over eight days ± 95% CI. Reproduced with permission from Zheng et al. (2012a).

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    Percentage of correct responses (A), incorrect responses (B) and omissions (C) for sham (open square) and BVD (closed square) rats after the animals reached the criterion. Data are expressed as mean ± SEM. Asterisks indicate significant differences. Reproduced with permission from Zheng et al. (2009b).

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    Mean time spent exploring familiar and novel objects in control, unilateral vestibular deafferentation (UVD) sham, UVD, BVD sham and BVD groups three (A) and six (B) months following the surgery. Data are expressed as mean ± SEM. Reproduced with permission from Zheng et al. (2004).

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    (A) Firing rate maps for the cells recorded over a six-week period. Control complex spiking cell. (B) Lesion complex spiking cell. Reproduced with permission from Russell et al. (2003b).

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    Firing rate maps recorded in the light–dark-light protocol in control (A) and lesioned (B) animals. The changes to the firing field that occurred in the dark were no greater than those in the light, for either control or lesioned animals. Therefore the observed changes to the lesioned animal’s firing field in the dark cannot be attributed to the absence of vision. Reproduced with permission from Russell et al. (2003b).

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    Power spectrum analysis of EEG from control and vestibular-lesioned animals. (A) Mean power spectral density (PSD) for each animal in the control and lesioned groups. The EEG recorded from the lesioned animals has relatively more broadband power at lower frequencies but a smaller peak at the theta frequency (8 Hz) relative to this background activity. (B) Mean normalized power and mean frequency relative to underlying broadband EEG at the energy peaks within the 6–9.5 and 9.5–13 Hz bands. Reproduced with permission from Russell et al. (2006).

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    (A) Distributions of the correlation coefficients generated by fitting a 6–9-Hz sinusoidal wave to all 1-s epochs of EEG for animals in the control and lesioned groups. A distribution was determined for each 10-min recording session and then averaged across all sessions to create a single distribution for each animal. EEG epochs tended to be less sinusoid-like in the lesioned animals. (B) Examples of 1-s epochs of ‘theta’ rhythm that had correlation coefficients of 0.1, 0.2, 0.4, 0.6, and 0.8 with a sine wave of 6–9 Hz (actual coefficients are displayed next to each waveform). Control group animals were almost four times more likely to generate an EEG epoch with a correlation of 0.6 or higher than were lesioned animals. Calibration bar: 0.2 mV. Reproduced with permission from Russell et al. (2006).

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    Representative EEG recordings from each of the control (C) and lesioned group (L) animals. Each continuous 30-s EEG recording is split into 2 15-s traces (top and bottom of each pair). Below each trace is a representation of the animal’s velocity at the corresponding time as a grey scale. The velocity trace is smoothed with a 1-s running average and darker regions indicate higher velocities. Note that theta rhythm is present in most of the EEG traces from the control animals, but less obvious or absent in the recordings from lesioned-group animals. Reproduced with permission from Russell et al. (2006).

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    Example of a significant decrease (p0.0001) in the number of basal dendritic intersections in the CA1 from rats with bilateral vestibular deafferentation (BVD) compared to sham-lesioned rats and control rats which did not undergo surgery. Unpublished preliminary data from Balabhadrapatruni, Zheng, Napper and Smith. This figure is published in colour in the online version.

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