Brain Structure and Function

, Volume 222, Issue 7, pp 3319–3332 | Cite as

Effects of bilateral vestibular deafferentation in rat on hippocampal theta response to somatosensory stimulation, acetylcholine release, and cholinergic neurons in the pedunculopontine tegmental nucleus

  • Phillip Aitken
  • Yiwen Zheng
  • Paul F. SmithEmail author
Original Article


Vestibular dysfunction has been shown to cause spatial memory impairment. Neurophysiological studies indicate that bilateral vestibular loss (BVL), in particular, is associated with an impairment of the response of hippocampal place cells and theta rhythm. However, the specific neural pathways through which vestibular information reaches the hippocampus are yet to be fully elucidated. The aim of the present study was to further investigate the hypothesised ‘theta-generating pathway’ from the brainstem vestibular nucleus to the hippocampus. BVL, and in some cases, unilateral vestibular loss (UVL), induced by intratympanic sodium arsanilate injections in rats, were used to investigate the effects of vestibular loss on somatosensory-induced type 2 theta rhythm, acetylcholine (ACh) release in the hippocampus, and the number of cholinergic neurons in the pedunculopontine tegmental nucleus (PPTg), an important part of the theta-generating pathway. Under urethane anaesthesia, BVL was found to cause a significant increase in the maximum power of the type 2 theta (3–6 Hz) frequency band compared to UVL and sham animals. Rats with BVL generally exhibited a lower basal level of ACh release than sham rats; however, this difference was not statistically significant. The PPTg of BVL rats exhibited significantly more choline-acetyltransferase (ChAT)-positive neurons than that of sham animals, as did the contralateral PPTg of UVL animals; however, the number of ChAT-positive neurons on the ipsilateral side of UVL animals was not significantly different from sham animals. The results of these studies indicate that parts of the theta-generating pathway undergo a significant reorganisation following vestibular loss, which suggests that this pathway is important for the interaction between the vestibular system and the hippocampus.


Bilateral vestibular lesions Hippocampus Acetylcholine Theta rhythm Pedunculopontine tegmental nucleus Rat 



This research was supported by grants from the University of Otago Research Committee and the Otago School of Medical Sciences Dean’s Bequest Fund. PA was supported by grants from the Helen Rosa Thacker Foundation, the Brain Health Research Centre, the George Duncan Memorial Scholarship, and the Hope Selwyn Scholarship. We thank the technical staff of the Dept. of Pathology, Dunedin School of Medicine, for their assistance with the temporal bone histology.


  1. Aitken P, Benoit A, Zheng Y, Philoxene B, Le Gall A, Denise P, Besnard S, Smith PF (2016) Hippocampal and striatal M1-muscarinic acetylcholine receptors are down-regulated following bilateral vestibular loss in rats. Hippocampus 26(12):1509–1514. doi: 10.1002/hipo.22651 CrossRefPubMedGoogle Scholar
  2. Aravamuthan BR, Angelaki DE (2012) Vestibular responses in the macaque pedunculopontine nucleus and central mesencephalic reticular formation. Neuroscience 223:183–199. doi: 10.1016/j.neuroscience.2012.07.054 CrossRefPubMedPubMedCentralGoogle Scholar
  3. Baek JH, Zheng YW, Darlington CL, Smith PF (2010) Evidence that spatial memory deficits following bilateral vestibular deafferentation in rats are probably permanent. Neurobiol Learn Mem 94(3):402–413. doi: 10.1016/j.nlm.2010.08.007 CrossRefPubMedGoogle Scholar
  4. Balabhadrapatruni S, Zheng Y, Napper R, Smith PF (2016) Basal dendritic length is reduced in the rat hippocampus following bilateral vestibular deafferentation. Neurobiol Learn Mem 131:56–60. doi: 10.1016/j.nlm.2016.03.009 CrossRefPubMedGoogle Scholar
  5. Bednarczyk MR, Aumont A, Decary S, Bergeron R, Fernandes KJ (2009) Prolonged voluntary wheel-running stimulates neural precursors in the hippocampus and forebrain of adult CD1 mice. Hippocampus 19(10):913–927. doi: 10.1002/hipo.20621 CrossRefPubMedGoogle Scholar
  6. Besnard S, Machado ML, Vignaux G, Boulouard M, Coquerel A, Bouet V, Freret T, Denise P, Lelong-Boulouard V (2012) Influence of vestibular input on spatial and nonspatial memory and on hippocampal NMDA receptors. Hippocampus 22(4):814–826. doi: 10.1002/hipo.20942 CrossRefPubMedGoogle Scholar
  7. Besnard S, Lopez C, Brandt T, Denise P, Smith PF (2015) Editorial: the vestibular system in cognitive and memory processes in mammalians. Front Integr Neurosci 9:55. doi: 10.3389/fnint.2015.00055 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Bigelow RT, Agrawal Y (2015) Vestibular involvement in cognition: Visuospatial ability, attention, executive function, and memory. J Vestib Res 25(2):73–89. doi: 10.3233/ves-150544 PubMedGoogle Scholar
  9. Bland BH (1986) The physiology and pharmacology of hippocampal formation theta rhythms. Prog Neurobiol 26(1):1–54. doi: 10.1016/0301-0082(86)90019-5 CrossRefPubMedGoogle Scholar
  10. Bland BH, Oddie SD (1998) Anatomical, electrophysiological and pharmacological studies of ascending brainstem hippocampal synchronizing pathways. Neurosci Biobehav Rev 22(2):259–273CrossRefPubMedGoogle Scholar
  11. Bland B, Seto M, Sinclair B, Fraser S (1984) The pharmacology of hippocampal theta cells: evidence that the sensory processing correlate is cholinergic. Brain Res 299(1):121CrossRefPubMedGoogle Scholar
  12. Boadas-Vaello P, Riera J, Llorens J (2005) Behavioral and pathological effects in the rat define two groups of neurotoxic nitriles. Toxicol Sci 88(2):456–466. doi: 10.1093/toxsci/kfi314 CrossRefPubMedGoogle Scholar
  13. Bocian R, Konopacki J (2001) Effect of posterior hypothalamic injection of procaine on the hippocampal theta rhythm in freely moving cats. Acta Neurobiol Exp (Wars) 61(2):125–134Google Scholar
  14. Brandt T, Schautzer F, Hamilton DA, Bruning R, Markowitsch HJ, Kalla R, Darlington C, Smith P, Strupp M (2005) Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans. Brain 128(11):2732–2741. doi: 10.1093/brain/awh617 CrossRefPubMedGoogle Scholar
  15. Bringmann A (1995) Different functions of rat’s pedunculopontine tegmental nucleus are reflected in cortical EEG. Neuroreport 6(15):2065–2068CrossRefPubMedGoogle Scholar
  16. Bringmann A (1997) Nicotine affects the occipital theta rhythm after lesion of the pedunculopontine tegmental nucleus in rats. NeuropsychoBiology 35(2):102–107CrossRefPubMedGoogle Scholar
  17. Carlson JD, Iacono RP, Maeda G (2004) Nociceptive excited and inhibited neurons within the pedunculopontine tegmental nucleus and cuneiform nucleus. Brain Res 1013(2):182–187. doi: 10.1016/j.brainres.2004.03.069 CrossRefPubMedGoogle Scholar
  18. Carlson JD, Selden NR, Heinricher MM (2005) Nocifensive reflex-related on- and off-cells in the pedunculopontine tegmental nucleus, cuneiform nucleus, and lateral dorsal tegmental nucleus. Brain Res 1063(2):187–194. doi: 10.1016/j.brainres.2005.09.036 CrossRefPubMedGoogle Scholar
  19. Cutfield NJ, Scott G, Waldman AD, Sharp DJ, Bronstein AM (2014) Visual and proprioceptive interaction in patients with bilateral vestibular loss. Neuroimage Clin 4:274–282. doi: 10.1016/j.nicl.2013.12.013 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cuthbert PC, Gilchrist DP, Hicks SL, MacDougall HG, Curthoys IS (2000) Electrophysiological evidence for vestibular activation of the guinea pig hippocampus. Neuroreport 11(7):1443–1447CrossRefPubMedGoogle Scholar
  21. Dudar JD, Whishaw IQ, Szerb JC (1979) Release of acetylcholine from the hippocampus of freely moving rats during sensory stimulation and running. Neuropharmacology 18(8–9):673–678CrossRefPubMedGoogle Scholar
  22. Gavrilov VV, Wiener SI, Berthoz A (1995) Enhanced hippocampal theta EEG during whole body rotations in awake restrained rats. Neurosci Lett 197(3):239–241. doi: 10.1016/0304-3940(95)11918-m CrossRefPubMedGoogle Scholar
  23. Gavrilov VV, Wiener SI, Berthoz A (1996) Whole-body rotations enhance hippocampal theta rhythmic slow activity in awake rats passively transported on a mobile robot. Ann N Y Acad Sci 781 (1 Lipids and Sy):385–398. doi: 10.1111/j.1749-6632.1996.tb15714.x CrossRefGoogle Scholar
  24. Givens B (1995) Low doses of ethanol impair spatial working memory and reduce hippocampal theta activity. Alcohol Clin Exp Res 19(3):763–767CrossRefPubMedGoogle Scholar
  25. Goddard M, Zheng Y, Darlington CL, Smith PF (2008) Locomotor and exploratory behavior in the rat following bilateral vestibular deafferentation. Behav Neurosci 122(2):448–459. doi: 10.1037/0735-7044.122.2.448 CrossRefPubMedGoogle Scholar
  26. Good CH, Bay KD, Buchanan R, Skinner RD, Garcia-Rill E (2007) Muscarinic and nicotinic responses in the developing pedunculopontine nucleus (PPN). Brain Res 1129(1):147–155. doi: 10.1016/j.brainres.2006.10.046 CrossRefPubMedGoogle Scholar
  27. Gottlich M, Jandl NM, Sprenger A, Wojak JF, Munte TF, Kramer UM, Helmchen C (2016) Hippocampal gray matter volume in bilateral vestibular failure. Hum Brain Mapp 37(5):1998–2006. doi: 10.1002/hbm.23152 CrossRefPubMedGoogle Scholar
  28. Harun A, Oh ES, Bigelow RT, Studenski S, Agrawal Y (2016) Vestibular impairment in dementia. Otol Neurotol 37(8):1137–1142. doi: 10.1097/MAO.0000000000001157 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hernandez-Chan NG, Gongora-Alfaro JL, Alvarez-Cervera FJ, Solis-Rodriguez FA, Heredia-Lopez FJ, Arankowsky-Sandoval G (2011) Quinolinic acid lesions of the pedunculopontine nucleus impair sleep architecture, but not locomotion, exploration, emotionality or working memory in the rat. Behav Brain Res 225(2):482–490. doi: 10.1016/j.bbr.2011.08.007 CrossRefPubMedGoogle Scholar
  30. Hitier M, Besnard S, Smith PF (2014) Vestibular pathways involved in cognition. Front Integr Neurosci 8 (59.10):59. doi: 10.3389/fnint.2014.00059 PubMedPubMedCentralGoogle Scholar
  31. Horii A, Takeda N, Mochizuki T, Okakura-Mochizuki K, Yamamoto Y, Yamatodani A (1994) Effects of vestibular stimulation on acetylcholine release from rat hippocampus: an in vivo microdialysis study. J Neurophysiol 72(2):605–611PubMedGoogle Scholar
  32. Horii A, Russell NA, Smith PF, Darlington CL, Bilkey DK (2004) Vestibular influences on CA1 neurons in the rat hippocampus: an electrophysiological study in vivo. Exp Brain Res 155(2):245–250. doi: 10.1007/s00221-003-1725-9 CrossRefPubMedGoogle Scholar
  33. Horowitz SS, Blanchard J, Morin LP (2005) Medial vestibular connections with the hypocretin (orexin) system. J Comp Neurol 487(2):127–146. doi: 10.1002/cne.20521 CrossRefPubMedGoogle Scholar
  34. Inglis F, Fibiger H (1995) Increases in hippocampal and frontal cortical acetylcholine release associated with presentation of sensory stimuli. Neuroscience 66(1):81–86CrossRefPubMedGoogle Scholar
  35. Jacob PY, Poucet B, Liberge M, Save E, Sargolini F (2014) Vestibular control of entorhinal cortex activity in spatial navigation. Front Integr Neurosci 8:38. doi: 10.3389/fnint.2014.00038 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Jones BE (1991) Paradoxical sleep and its chemical/structural substrates in the brain. Neuroscience 40(3):637–656CrossRefPubMedGoogle Scholar
  37. Jones BE, Beaudet A (1987) Distribution of acetylcholine and catecholamine neurons in the cat brainstem: a choline acetyltransferase and tyrosine hydroxylase immunohistochemical study. J Comp Neurol 261(1):15–32. doi: 10.1002/cne.902610103 CrossRefPubMedGoogle Scholar
  38. Jurkowlaniec E, Tokarski J, Trojniar W (2003) Effect of unilateral ibotenate lesions of the ventral tegmental area on cortical and hippocampal EEG in freely behaving rats. Acta Neurobiol Exp (Wars) 63(4):369–375Google Scholar
  39. Kang Y, Kitai ST (1990) Electrophysiological properties of pedunculopontine neurons and their postsynaptic responses following stimulation of substantia nigra reticulata. Brain Res 535(1):79–95. doi: 10.1016/0006-8993(90)91826-3 CrossRefPubMedGoogle Scholar
  40. Keuker JIH, Vollmann-Honsdorf GK, Fuchs E (2001) How to use the optical fractionator: an example based on the estimation of neurons in the hippocampal CA1 and CA3 regions of tree shrews. Brain Res Protoc 7 (3):211–221. doi:  10.1016/S1385-299x(01)00064-2 CrossRefGoogle Scholar
  41. Kirby SL, Harvey RE, Goebel EA, Koppen JR, Wallace DG, Yoder RM (2013) Head direction signal degradation impairs spatial learning. Paper presented at the Society for Neuroscience, San Diago, CAGoogle Scholar
  42. Kirk IJ (1998) Frequency modulation of hippocampal theta by the supramammillary nucleus, and other hypothalamo-hippocampal interactions: mechanisms and functional implications. Neurosci Biobehav Rev 22(2):291–302CrossRefPubMedGoogle Scholar
  43. Kobayashi T, Homma Y, Good C, Skinner RD, Garcia-Rill E (2003) Developmental changes in the effects of serotonin on neurons in the region of the pedunculopontine nucleus. Brain Res Dev Brain Res 140(1):57–66. doi: 10.1016/S0165-3806(02)00575-8 CrossRefPubMedGoogle Scholar
  44. Kobayashi T, Good C, Biedermann J, Barnes C, Skinner RD, Garcia-Rill E (2004) Developmental changes in pedunculopontine nucleus (PPN) neurons. J Neurophysiol 91(4):1470–1481. doi: 10.1152/jn.01024.2003 CrossRefPubMedGoogle Scholar
  45. Kremmyda O, Hufner K, Flanagin VL, Hamilton DA, Linn J, Strupp M, Jahn K, Brandt T (2016) Beyond dizziness: virtual navigation, spatial anxiety and hippocampal volume in bilateral vestibulopathy. Front Hum Neurosci 10:139. doi: 10.3389/fnhum.2016.00139 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Kuczynski B, Kolakowsky-Hayner SA (2011) Autoreceptor. In: Kreutzer JS, DeLuca J, Caplan B (eds) Encyclopedia of clinical neuropsychology. Springer, New York, NY, pp 333–333. doi: 10.1007/978-0-387-79948-3_1731
  47. Leszkowicz E, Kusmierczak M, Matulewicz P, Trojniar W (2007) Modulation of hippocampal theta rhythm by the opioid system of the pedunculopontine tegmental nucleus. Acta Neurobiol Exp 67:447–460Google Scholar
  48. Leutgeb S, Mizumori SJ (1999) Excitotoxic septal lesions result in spatial memory deficits and altered flexibility of hippocampal single-unit representations. J Neurosci 19(15):6661–6672PubMedGoogle Scholar
  49. Lopez C (2016) The vestibular system: balancing more than just the body. Curr Opin Neurol 29(1):74–83. doi: 10.1097/WCO.0000000000000286 CrossRefPubMedGoogle Scholar
  50. Matulewicz P, Kuśmierczak M, Orzeł-Gryglewska J, Jurkowlaniec E (2013) Hippocampal theta rhythm induced by rostral pontine nucleus stimulation in the conditions of pedunculopontine tegmental nucleus inactivation. Brain Res Bull 96:10–18CrossRefPubMedGoogle Scholar
  51. MBF- Bioscience (2016) The optical fractionator. Accessed 18 Nov 2016
  52. McCulloch CE, Searle SR, Neuhaus JM (2008) Generalized, Linear, and Mixed Models. 2nd edn. Wiley, Hoboken, NJGoogle Scholar
  53. Mizuno T, Endo Y, Arita J, Kimura F (1991) Acetylcholine release in the rat hippocampus as measured by the microdialysis method correlates with motor activity and exhibits a diurnal variation. Neuroscience 44(3):607–612. doi: 10.1016/0306-4522(91)90081-x CrossRefPubMedGoogle Scholar
  54. Monmaur P, Collet A, Puma C, Frankel-Kohn L, Sharif A (1997) Relations between acetylcholine release and electrophysiological characteristics of theta rhythm: a microdialysis study in the urethane-anesthetized rat hippocampus. Brain Res Bull 42(2):141–146. doi: 10.1016/s0361-9230(96)00200-6 CrossRefPubMedGoogle Scholar
  55. Neo P, Carter D, Zheng Y, Smith P, Darlington C, McNaughton N (2012) Septal elicitation of hippocampal theta rhythm did not repair cognitive and emotional deficits resulting from vestibular lesions. Hippocampus 22(5):1176–1187. doi: 10.1002/hipo.20963 CrossRefPubMedGoogle Scholar
  56. Nowacka A, Jurkowlaniec E, Trojniar W (2002) Microinjection of procaine into the pedunculopontine tegmental nucleus suppresses hippocampal theta rhythm in urethane-anesthetized rats. Brain Res Bull 58(4):377–384. doi: 10.1016/S0361-9230(02)00801-8 CrossRefPubMedGoogle Scholar
  57. Nunez A, Rodrigo-Angulo ML, De Andres I, Reinoso-Suarez F (2002) Firing activity and postsynaptic properties of morphologically identified neurons of ventral oral pontine reticular nucleus. Neuroscience 115(4):1165–1175. doi: 10.1016/S0306-4522(02)00478-5 CrossRefPubMedGoogle Scholar
  58. O’Keefe J (1993) Hippocampus, theta, and spatial memory. Curr Opin Neurobiol 3(6):917–924CrossRefPubMedGoogle Scholar
  59. Orzel-Gryglewska J, Jurkowlaniec E, Trojniar W (2006) Microinjection of procaine and electrolytic lesion in the ventral tegmental area suppresses hippocampal theta rhythm in urethane-anesthetized rats. Brain Res Bull 68(5):295–309. doi: 10.1016/j.brainresbull.2005.08.026 CrossRefPubMedGoogle Scholar
  60. Orzel-Gryglewska J, Matulewicz P, Jurkowlaniec E (2015) Brainstem system of hippocampal theta induction: the role of the ventral tegmental area. Synapse 69(11):553–575. doi: 10.1002/syn.21843 CrossRefPubMedGoogle Scholar
  61. Ossenkopp KP, Eckel LA, Hargreaves EL, Kavaliers M (1992) Sodium arsanilate-induced vestibular dysfunction in meadow voles (Microtus pennsylvanicus): effects on posture, spontaneous locomotor activity and swimming behavior. Behav Brain Res 47(1):13–22. doi: 10.1016/S0166-4328(05)80248-7 CrossRefPubMedGoogle Scholar
  62. Pignatelli M, Beyeler A, Leinekugel X (2012) Neural circuits underlying the generation of theta oscillations. J Physiol Paris 106(3–4):81–92. doi: 10.1016/j.jphysparis.2011.09.007 CrossRefPubMedGoogle Scholar
  63. Porter JD, Pellis SM, Meyer ME (1990) An open-field activity analysis of labyrinthectomized rats. Physiol Behav 48(1):27–30. doi: 10.1016/0031-9384(90)90255-3 CrossRefPubMedGoogle Scholar
  64. Previc FH (2013) Vestibular loss as a contributor to Alzheimer’s disease. Med Hypotheses 80(4):360–367. doi: 10.1016/j.mehy.2012.12.023 CrossRefPubMedGoogle Scholar
  65. Rancz EA, Moya J, Drawitsch F, Brichta AM, Canals S, Margrie TW (2015) Widespread vestibular activation of the rodent cortex. J Neurosci 35(15):5926–5934. doi: 10.1523/JNEUROSCI.1869-14.2015 CrossRefPubMedPubMedCentralGoogle Scholar
  66. Ransmayr G, Faucheux B, Nowakowski C, Kubis N, Federspiel S, Kaufmann W, Henin D, Hauw J-J, Agid Y, Hirsch E (2000) Age-related changes of neuronal counts in the human pedunculopontine nucleus. Neurosci Lett 288(3):195–198CrossRefPubMedGoogle Scholar
  67. Richards MH (1990) Rat hippocampal muscarinic autoreceptors are similar to the M2 (cardiac) subtype: comparison with hippocampal M1, atrial M2 and ileal M3 receptors. Br J Pharmacol 99(4):753–761CrossRefPubMedPubMedCentralGoogle Scholar
  68. Russell N, Horii A, Smith P, Darlington C, Bilkey D (2003a) Effects of bilateral vestibular deafferentation on radial arm maze performance. J Vestib Res 13:9–16PubMedGoogle Scholar
  69. Russell NA, Horii A, Smith PF, Darlington CL, Bilkey DK (2003b) Long-term effects of permanent vestibular lesions on hippocampal spatial firing. J Neurosci 23(16):6490–6498PubMedGoogle Scholar
  70. Russell NA, Horii A, Smith PF, Darlington CL, Bilkey DK (2006) Lesions of the vestibular system disrupt hippocampal theta rhythm in the rat. J Neurophysiol 96(1):4–14. doi: 10.1152/jn.00953.2005 CrossRefPubMedGoogle Scholar
  71. Seemungal B, Yousif N, Bronstein AM, Naushahi J, Nandi D (2010) POD06 human pedunculopontine nucleus displays vestibular reactivity. J Neurol Neurosurg Psychiatry 81(11):e43–e43. doi: 10.1136/jnnp.2010.226340.106 Google Scholar
  72. Semba K, Fibiger HC (1992) Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study. J Comp Neurol 323(3):387–410. doi: 10.1002/cne.903230307 CrossRefPubMedGoogle Scholar
  73. Seo YJ, Kim J, Kim SH (2016) The change of hippocampal volume and its relevance with inner ear function in Meniere’s disease patients. Auris Nasus Larynx 43(6):620–625. doi: 10.1016/j.anl.2016.01.006 CrossRefPubMedGoogle Scholar
  74. Shin J (2010) Passive rotation-induced theta rhythm and orientation homeostasis response. Synapse 64(5):409–415. doi: 10.1002/syn.20742 CrossRefPubMedGoogle Scholar
  75. Shiromani PJ, Armstrong DM, Berkowitz A, Jeste DV, Gillin JC (1988) Distribution of choline acetyltransferase immunoreactive somata in the feline brainstem: implications for REM sleep generation. Sleep 11(1):1–16CrossRefPubMedGoogle Scholar
  76. Smith PF, Curthoys IS. (1989) Mechanisms of recovery from unilateral labyrinthectomy: a review. Brain Res Revs 14: 155–180.CrossRefGoogle Scholar
  77. Smith PF (2012) A note on the advantages of using linear mixed model analysis with maximal likelihood estimation over repeated measures ANOVAs in psychopharmacology: comment on Clark et al. (2012). J Psychopharmacol 26(12):1605–1607. doi: 10.1177/0269881112463471 CrossRefPubMedGoogle Scholar
  78. Sprent P, Smeeton NC (2007) Applied Nonparametric Statistical Methods. CRC Press, Boca RatonGoogle Scholar
  79. Stackman RW, Clark AS, Taube JS (2002) Hippocampal spatial representations require vestibular input. Hippocampus 12(3):291–303. doi: 10.1002/hipo.1112 CrossRefPubMedPubMedCentralGoogle Scholar
  80. Stiles L, Zheng Y, Darlington CL, Smith PF (2012) The D(2) dopamine receptor and locomotor hyperactivity following bilateral vestibular deafferentation in the rat. Behav Brain Res 227(1):150–158. doi: 10.1016/j.bbr.2011.11.006 CrossRefPubMedGoogle Scholar
  81. Tai SK, Ma J, Ossenkopp KP, Leung LS (2012) Activation of immobility-related hippocampal theta by cholinergic septohippocampal neurons during vestibular stimulation. Hippocampus 22(4):914–925. doi: 10.1002/hipo.20955 CrossRefPubMedGoogle Scholar
  82. Takakusaki K, Kitai ST (1997) Ionic mechanisms involved in the spontaneous firing of tegmental pedunculopontine nucleus neurons of the rat. Neuroscience 78(3):771–794. doi: 10.1016/S0306-4522(96)00540-4 CrossRefPubMedGoogle Scholar
  83. Takakusaki K, Shiroyama T, Kitai ST (1997) Two types of cholinergic neurons in the rat tegmental pedunculopontine nucleus: electrophysiological and morphological characterization. Neuroscience 79(4):1089–1109CrossRefPubMedGoogle Scholar
  84. Takano Y, Hanada Y (2009) The driving system for hippocampal theta in the brainstem: an examination by single neuron recording in urethane-anesthetized rats. Neurosci Lett 455(1):65–69. doi: 10.1016/j.neulet.2009.03.028 CrossRefPubMedGoogle Scholar
  85. Van Cruijsen N, Hiemstra WM, Meiners LC, Wit HP, Albers FW (2007) Hippocampal volume measurement in patients with Meniere’s disease: a pilot study. Acta Otolaryngol 127(10):1018–1023. doi: 10.1080/00016480601127000 CrossRefPubMedGoogle Scholar
  86. Vandecasteele M, Varga V, Berényi A, Papp E, Barthó P, Venance L, Freund TF, Buzsáki G (2014) Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus. Proc Natl Acad Sci USA 111(37):13535–13540CrossRefPubMedPubMedCentralGoogle Scholar
  87. Vertes RP, Kocsis B (1997) Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81(4):893–926CrossRefPubMedGoogle Scholar
  88. Vertes RP, Martin GF (1988) Autoradiographic analysis of ascending projections from the pontine and mesencephalic reticular formation and the median raphe nucleus in the rat. J Comp Neurol 275(4):511–541. doi: 10.1002/cne.902750404 CrossRefPubMedGoogle Scholar
  89. Vignaux G, Chabbert C, Gaboyard-Niay S, Travo C, Machado ML, Denise P, Comoz F, Hitier M, Landemore G, Philoxene B, Besnard S (2012) Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats. Toxicol Appl Pharmacol 258(1):61–71. doi: 10.1016/j.taap.2011.10.008 CrossRefPubMedGoogle Scholar
  90. West MJ, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231(4):482–497. doi:DOI: 10.1002/ar.1092310411 CrossRefPubMedGoogle Scholar
  91. Winson J (1978) Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. Science 201(4351):160–163CrossRefPubMedGoogle Scholar
  92. Wise DD, Barkhimer TV, Brault PA, Kirchhoff JR, Messer WS Jr, Hudson RA (2002) Internal standard method for the measurement of choline and acetylcholine by capillary electrophoresis with electrochemical detection. J Chromatogr B Anal Technol Biomed Life Sci 775(1):49–56CrossRefGoogle Scholar
  93. Woodnorth MA, Kyd RJ, Logan BJ, Long MA, McNaughton N (2003) Multiple hypothalamic sites control the frequency of hippocampal theta rhythm. Hippocampus 13(3):361–374. doi: 10.1002/hipo.10111 CrossRefPubMedGoogle Scholar
  94. Yoder RM, Pang KC (2005) Involvement of GABAergic and cholinergic medial septal neurons in hippocampal theta rhythm. Hippocampus 15(3):381–392. doi: 10.1002/hipo.20062 CrossRefPubMedGoogle Scholar
  95. Zhang YF, Sato G, Hitier M, Zheng Y, Denise P, Besnard S, Smith PF (2013) Functional relations between the vestibular system and hippocampus. In: Paper presented at the Australasian Winter Conference on Brain Research, QueenstownGoogle Scholar
  96. Zheng Y, Balabhadrapatruni S, Baek JH, Chung P, Gliddon C, Zhang M, Darlington CL, Napper R, Strupp M, Brandt T, Smith PF (2012) The effects of bilateral vestibular loss on hippocampal volume, neuronal number, and cell proliferation in rats. Front Neurol 3:20. doi: 10.3389/fneur.2012.00020 PubMedPubMedCentralGoogle Scholar
  97. zu Eulenburg P, Stoeter P, Dieterich M (2010) Voxel-based morphometry depicts central compensation after vestibular neuritis. Ann Neurol 68(2):241–249. doi: 10.1002/ana.22063 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Phillip Aitken
    • 1
  • Yiwen Zheng
    • 1
    • 2
    • 3
  • Paul F. Smith
    • 1
    • 2
    • 3
    Email author
  1. 1.Department of Pharmacology and Toxicology, School of Biomedical Sciences, and Brain Health Research CentreUniversity of OtagoDunedinNew Zealand
  2. 2.Brain Research New Zealand Centre of Research ExcellenceUniversity of AucklandAucklandNew Zealand
  3. 3.The Eisdell Moore Centre for Hearing and Balance ResearchUniversity of AucklandAucklandNew Zealand

Personalised recommendations