Lesions of the vestibular system disrupt hippocampal theta rhythm in the rat.

The hippocampus has a major role in memory for spatial location. Theta is a rhythmic hippocampal EEG oscillation that occurs at approximately 8 Hz during voluntary movement and that may have some role in encoding spatial information. We investigated whether, as part of this process, theta might be influenced by self-movement signals provided by the vestibular system. The effects of bilateral peripheral vestibular lesions, made > or = 60 days prior to recording, were assessed in freely moving rats. Power spectral analysis revealed that theta in the lesioned animals had a lower power and frequency compared with that recorded in the control animals. When the electroencephalography (EEG) was compared in epochs matched for speed of movement and acceleration, theta was less rhythmic in the lesioned group, indicating that the effect was not a result of between-group differences in this behavior. Blood measurements of corticosterone were also similar in the two groups indicating that the results could not be attributed to changes in stress levels. Despite the changes in theta EEG, individual neurons in the CA1 region of lesioned animals continued to fire with a periodicity of approximately 8 Hz. The positive correlation between cell firing rate and movement velocity that is observed in CA1 neurons of normal animals was also maintained in cells recorded from lesion group animals. These findings indicate that although vestibular signals may contribute to theta rhythm generation, velocity-related firing in hippocampal neurons is dependent on nonvestibular signals such as sensory flow, proprioception, or motor efference copy.

[1]  J. Taube,et al.  Processing the head direction cell signal: A review and commentary , 1996, Brain Research Bulletin.

[2]  G. V. Goddard,et al.  Medial septal facilitation of hippocampal granule cell activity is mediated by inhibition of inhibitory interneurones , 1985, Brain Research.

[3]  J. Gray The neuropsychology of anxiety. , 1985, Issues in mental health nursing.

[4]  G Buzsáki,et al.  Sustained activation of hippocampal pyramidal cells by ‘space clamping’ in a running wheel , 1999, The European journal of neuroscience.

[5]  P. Vidal,et al.  The differential response of astrocytes within the vestibular and cochlear nuclei following unilateral labyrinthectomy or vestibular afferent activity blockade by transtympanic tetrodotoxin injection in the rat , 2005, Neuroscience.

[6]  T. Deboer,et al.  Electroencephalogram theta frequency changes in parallel with euthermic brain temperature , 2002, Brain Research.

[7]  John O'Keefe,et al.  Independent rate and temporal coding in hippocampal pyramidal cells , 2003, Nature.

[8]  B. Wyble,et al.  Analysis of theta power in hippocampal EEG during bar pressing and running behavior in rats during distinct behavioral contexts , 2004, Hippocampus.

[9]  Paul F. Smith,et al.  Vestibular–hippocampal interactions , 1997, Hippocampus.

[10]  J. Gray,et al.  Précis of The neuropsychology of anxiety: An enquiry into the functions of the septo-hippocampal system , 1982, Behavioral and Brain Sciences.

[11]  P. Teitelbaum,et al.  Deafferentation of the vestibular organ: Effects on atropine-resistant EEG in rats , 1989 .

[12]  J. Taube,et al.  Firing Properties of Head Direction Cells in the Rat Anterior Thalamic Nucleus: Dependence on Vestibular Input , 1997, The Journal of Neuroscience.

[13]  H. Kiyama,et al.  Effects of MK801 on Fos expression in the rat brainstem after unilateral labyrinthectomy , 1995, Brain Research.

[14]  W E Skaggs,et al.  Deciphering the hippocampal polyglot: the hippocampus as a path integration system. , 1996, The Journal of experimental biology.

[15]  L. Leung Theta rhythm during REM sleep and waking: correlations between power, phase and frequency. , 1984, Electroencephalography and clinical neurophysiology.

[16]  P E Sharp,et al.  Influences of vestibular and visual motion information on the spatial firing patterns of hippocampal place cells , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  P. Fuller,et al.  Neurovestibular modulation of circadian and homeostatic regulation: Vestibulohypothalamic connection? , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  David K Bilkey,et al.  Bilateral peripheral vestibular lesions produce long-term changes in spatial learning in the rat. , 2003, Journal of vestibular research : equilibrium & orientation.

[19]  O. Hermanson,et al.  Evidence for vestibular regulation of autonomic functions in a mouse genetic model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[21]  C. Boast,et al.  Motor activity changes following cerebral ischemia in gerbils are correlated with the degree of neuronal degeneration in hippocampus. , 1988, Behavioral neuroscience.

[22]  K. Zyo,et al.  Neuroanatomical study of afferent projections to the supramammillary nucleus of the rat , 1993, Anatomy and Embryology.

[23]  I. Whishaw Place Learning in Hippocampal Rats and the Path Integration Hypothesis , 1998, Neuroscience & Biobehavioral Reviews.

[24]  I. Gartside,et al.  Relationship Between Venous Pressure and tissue Volume During Venous Congestion Plethysmography in Man , 1997, The Journal of physiology.

[25]  David K Bilkey,et al.  A low cost, high precision subminiature microdrive for extracellular unit recording in behaving animals , 1999, Journal of Neuroscience Methods.

[26]  S. Mizumori,et al.  Excitotoxic Septal Lesions Result in Spatial Memory Deficits and Altered Flexibility of Hippocampal Single-Unit Representations , 1999, The Journal of Neuroscience.

[27]  I. Curthoys,et al.  Mechanisms of recovery following unilateral labyrinthectomy: a review , 1989, Brain Research Reviews.

[28]  Michael Colombo,et al.  A lightweight microdrive for single-unit recording in freely moving rats and pigeons. , 2003, Methods.

[29]  B. H. Bland The physiology and pharmacology of hippocampal formation theta rhythms , 1986, Progress in Neurobiology.

[30]  J. Rawlins,et al.  The time course of the hyperactivity that follows lesions or temporary inactivation of the fimbria-fornix , 2001, Behavioural Brain Research.

[31]  Noah A. Russell,et al.  Long-Term Effects of Permanent Vestibular Lesions on Hippocampal Spatial Firing , 2003, The Journal of Neuroscience.

[32]  Alain Berthoz,et al.  Enhanced hippocampal theta EEG during whole body rotations in awake restrained rats , 1995, Neuroscience Letters.

[33]  J. B. Ranck,et al.  Hippocampal theta rhythm and the firing of neurons in walking and urethane anesthetized rats , 2004, Experimental Brain Research.

[34]  Paul F. Smith,et al.  Activation of the hypothalamic–pituitary–adrenal axis following vestibular deafferentation in pigmented guinea pig , 2003, Brain Research.

[35]  B. McNaughton,et al.  The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats , 1983, Experimental Brain Research.

[36]  G. Buzsáki Theta Oscillations in the Hippocampus , 2002, Neuron.

[37]  L. Leung Pharmacology of theta phase shift in the hippocampal CA1 region of freely moving rats. , 1984, Electroencephalography and clinical neurophysiology.

[38]  David K Bilkey,et al.  Theta‐ and movement velocity‐related firing of hippocampal neurons is disrupted by lesions centered on the perirhinal cortex , 2003, Hippocampus.

[39]  J. Zimmer,et al.  Postischemic hyperactivity in the Mongolian gerbil correlates with loss of hippocampal neurons. , 1997, Behavioral neuroscience.

[40]  David K Bilkey,et al.  The dynamic nature of spatial encoding in the hippocampus. , 2005, Behavioral neuroscience.

[41]  B. McNaughton,et al.  Self-Motion and the Hippocampal Spatial Metric , 2005, The Journal of Neuroscience.

[42]  A Berthoz,et al.  Whole‐Body Rotations Enhance Hippocampal Theta Rhythmic Slow Activity in Awake Rats Passively Transported on a Mobile Robot a , 1996, Annals of the New York Academy of Sciences.

[43]  G. Buzsáki,et al.  Hippocampal theta activity following selective lesion of the septal cholinergic systeM , 1994, Neuroscience.

[44]  P. Sheard,et al.  Adrenalectomy‐induced cell death in the dentate gyrus: Further characterisation using TUNEL and effects of the Ginkgo biloba extract, EGb 761, and ginkgolide B , 2003, Hippocampus.

[45]  B. H. Bland,et al.  Hippocampal Formation Theta Activity and Movement Selection , 1998, Neuroscience & Biobehavioral Reviews.

[46]  F. H. Lopes da Silva,et al.  Spectral characteristics of the hippocampal EEG in the freely moving rat. , 1982, Electroencephalography and clinical neurophysiology.

[47]  Theodore Raphan,et al.  The vestibulo-ocular reflex in three dimensions , 2002, Experimental Brain Research.

[48]  Thomas Brandt,et al.  Spatial Memory Deficits in Patients with Chronic Bilateral Vestibular Failure , 2003, Annals of the New York Academy of Sciences.

[49]  J. Furman,et al.  Psychiatric consequences of vestibular dysfunction. , 2001, Current opinion in neurology.

[50]  David K Bilkey,et al.  Ten- to 12-Hz EEG oscillation in the rat hippocampus and rhinal cortex that is modulated by environmental familiarity. , 2005, Journal of neurophysiology.

[51]  E Godaux,et al.  Neuronal activity in the vestibular nuclei after contralateral or bilateral labyrinthectomy in the alert guinea pig. , 1998, Journal of neurophysiology.

[52]  Paul F. Smith,et al.  Cytosolic glucocorticoid receptor expression in the rat vestibular nucleus and hippocampus following unilateral vestibular deafferentation , 2005, Experimental Brain Research.

[53]  I S Curthoys,et al.  Electrophysiological evidence for vestibular activation of the guinea pig hippocampus , 2000, Neuroreport.

[54]  T. Freund,et al.  GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus , 1988, Nature.

[55]  Cynthia L. Darlington,et al.  Vestibular influences on CA1 neurons in the rat hippocampus: an electrophysiological study in vivo , 2004, Experimental Brain Research.

[56]  H. Ishizuka,et al.  Immunoelectron microscopic observations of hypothalamic TRH-containing neurons in rats , 2004, Experimental Brain Research.

[57]  T. Freund,et al.  Disinhibition of rat hippocampal pyramidal cells by GABAergic afferents from the septum. , 1997, The Journal of physiology.

[58]  Paul F. Smith,et al.  Immunocytochemical and stereological study of glucocorticoid receptors in rat medial vestibular nucleus neurons and the effects of unilateral vestibular deafferentation , 2005, Acta oto-laryngologica.

[59]  R. Vertes,et al.  Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. , 1997, Neuroscience.

[60]  T. Brandt,et al.  Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans. , 2005, Brain : a journal of neurology.

[61]  T. Kubo,et al.  Microarray analysis of gene expression in the rat vestibular nucleus complex following unilateral vestibular deafferentation , 2004, Journal of neurochemistry.

[62]  L. Kellényi,et al.  Laminar distribution of hippocampal rhythmic slow activity (RSA) in the behaving rat: Current-source density analysis, effects of urethane and atropine , 1986, Brain Research.

[63]  R. Muller,et al.  The Effects on Place Cells of Local Scopolamine Dialysis Are Mimicked by a Mixture of Two Specific Muscarinic Antagonists , 2004, The Journal of Neuroscience.

[64]  Stan Leung Lai-Wo Pharmacology of theta phase shift in the hippocampal CA1 region of freely moving rats , 1984 .

[65]  G. Viana di Prisco,et al.  Theta rhythm of the hippocampus: subcortical control and functional significance. , 2004, Behavioral and cognitive neuroscience reviews.

[66]  G. A. Howell,et al.  Hippocampal EEG in normal mice and in mice with congenital vestibular defects. , 1982, Behavioral and neural biology.

[67]  B. McNaughton,et al.  Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences , 1996, Hippocampus.

[68]  G Krinke,et al.  Impaired tunnel-maze behavior in rats with sensory lesions: vestibular and auditory systems. , 1991, Neurotoxicology.

[69]  H. Fibiger,et al.  Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat , 1988, The Journal of comparative neurology.

[70]  Alan M. Brichta,et al.  Dizocilpine attenuates streptomycin-induced vestibulotoxicity in rats , 1999, Neuroscience Letters.

[71]  T. Kubo,et al.  Effects of unilateral labyrinthectomy on GAD, GAT1 and GABA receptor gene expression in the rat vestibular nucleus , 2003, Neuroreport.

[72]  John D. Aitchison,et al.  Optic Flow Input to the Hippocampal Formation from the Accessory Optic System , 1999, The Journal of Neuroscience.

[73]  Y. Yamamoto,et al.  Effects of vestibular stimulation on acetylcholine release from rat hippocampus: an in vivo microdialysis study. , 1994, Journal of neurophysiology.

[74]  N. McNaughton,et al.  Supramammillary cell firing and hippocampal rhythmical slow activity. , 1991, Neuroreport.

[75]  Paul F. Smith,et al.  Does vestibular damage cause cognitive dysfunction in humans? , 2005, Journal of vestibular research : equilibrium & orientation.

[76]  L W Leung,et al.  Model of gradual phase shift of theta rhythm in the rat. , 1984, Journal of neurophysiology.

[77]  J. O’Keefe,et al.  Phase relationship between hippocampal place units and the EEG theta rhythm , 1993, Hippocampus.

[78]  B. H. Bland,et al.  Extrinsic and intrinsic properties underlying oscillation and synchrony in limbic cortex , 1993, Progress in Neurobiology.

[79]  Douglas G Wallace,et al.  Vestibular Information Is Required for Dead Reckoning in the Rat , 2002, The Journal of Neuroscience.

[80]  J Bures,et al.  Place cells and place navigation. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[81]  J. Aggleton,et al.  The mammillary bodies: two memory systems in one? , 2004, Nature Reviews Neuroscience.

[82]  B. McNaughton,et al.  Reversible inactivation of the medial septum: selective effects on the spontaneous unit activity of different hippocampal cell types , 1989, Brain Research.

[83]  F. L. D. Silva,et al.  Hippocampal EEG and motor activity in the cat: The role of eye movements and body acceleration , 1984, Behavioural Brain Research.

[84]  Neil McNaughton,et al.  The medial supramammillary nucleus, spatial learning and the frequency of hippocampal theta activity , 1997, Brain Research.

[85]  Attila I Gulyás,et al.  Convergence of excitatory and inhibitory inputs onto CCK‐containing basket cells in the CA1 area of the rat hippocampus , 2004, The European journal of neuroscience.

[86]  J. Taube,et al.  Hippocampal spatial representations require vestibular input , 2002, Hippocampus.

[87]  R. Muller,et al.  Muscarinic Blockade Slows and Degrades the Location-Specific Firing of Hippocampal Pyramidal Cells , 2003, The Journal of Neuroscience.