The Cerebellum

, Volume 16, Issue 2, pp 398–410 | Cite as

Electrical Stimulation Normalizes c-Fos Expression in the Deep Cerebellar Nuclei of Depressive-like Rats: Implication of Antidepressant Activity

Original Paper
First Online:

Abstract

The electrical stimulation of specific brain targets has been shown to induce striking antidepressant effects. Despite that recent data have indicated that cerebellum is involved in emotional regulation, the mechanisms by which stimulation improved mood-related behaviors in the cerebellum remained largely obscure. Here, we investigated the stimulation effects of the ventromedial prefrontal cortex (vmPFC), nucleus accumbens (NAc), and lateral habenular nucleus on the c-Fos neuronal activity in various deep cerebellar and vestibular nuclei using the unpredictable chronic mild stress (CMS) animal model of depression. Our results showed that stressed animals had increased number of c-Fos cells in the cerebellar dentate and fastigial nuclei, as well as in the spinal vestibular nucleus. To examine the stimulation effects, we found that vmPFC stimulation significantly decreased the c-Fos activity within the cerebellar fastigial nucleus as compared to the CMS sham. Similarly, there was also a reduction of c-Fos expression in the magnocellular part of the medial vestibular nucleus in vmPFC- and NAc core-stimulated animals when compared to the CMS sham. Correlational analyses showed that the anxiety measure of home-cage emergence escape latency was positively correlated with the c-Fos neuronal activity of the cerebellar fastigial and magnocellular and parvicellular parts of the interposed nuclei in CMS vmPFC-stimulated animals. Interestingly, there was a strong correlation among activation in these cerebellar nuclei, indicating that the antidepressant-like behaviors were possibly mediated by the vmPFC stimulation-induced remodeling within the forebrain-cerebellar neurocircuitry.

Keywords

High-frequency stimulation Ventromedial prefrontal cortex Deep cerebellar nuclei Vestibular nuclei Antidepressant-like behaviors 

Abbreviations

CMS

Chronic mild stress

Dent

Dentate nucleus of the cerebellum

Fast

Fastigial cerebellar nucleus

HCET

Home-cage emergence test

HFS

High-frequency stimulation

IntMC

Interposed cerebellar nucleus, magnocellular part

IntPC

Interposed cerebellar nucleus, parvicellular part

LHb

Lateral habenular nucleus

MVePC

Medial vestibular nucleus, parvicellular part

MVeMC

Medial vestibular nucleus, magnocellular part

NAc core

Nucleus accumbens core

NAc shell

Nucleus accumbens shell

SpVe

Spinal vestibular nucleus

vmPFC

Ventromedial prefrontal cortex

This is a preview of subscription content, log in to check access.

Notes

Acknowledgments

The authors are thankful to Gara Lopez and Maria Ruiz for technical assistance in histochemical works. The scientific works were funded by the Netherlands Organization for Scientific Research (NWO-VENI no. 016.096.032), the University of Hong Kong Seed Funding Program for Basic Research (201604159006), and the Hong Kong UGC-ECS Grant (27104616).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

12311_2016_812_MOESM1_ESM.doc (81 kb)
Supplementary Table 1 (a) shows the groups and the number of animals used for the non-CMS and CMS treatment conditions. Animals were implanted with stimulating electrodes in the vmPFC, NAc core, NAc shell, and LHb based on the rat brain atlas of Paxinos and Watson [43]. (b) shows the significant effects of data analyzed by a multivariate General Linear Model to determine the within- and between-subjects factor groups, as well as oneway ANOVA with Bonferroni post hoc tests for detailed multiple comparisons. All p values < 0.05 were considered statistically significance. (c) shows the significant effects of data comparison between the individual stimulated-group and sham animals. The data were analyzed by independent sample t-test, and all p values < 0.05 were considered statistically significance. (DOC 81 kb)
12311_2016_812_MOESM2_ESM.doc (222 kb)
Supplementary Table 2 The tables show the Pearson correlation coefficients between variables related with the antidepressant-like behaviors and the c-Fos neuronal activities within the deep cerebellar and vestibular nuclei. The tables display correlations for sham groups (a), and animals subject to high-frequency stimulation of the vmPFC (b), NAc core (c), NAc shell (d), and the LHb (e). The lower-left side of the tables shows correlations of non-CMS animals, while the upper-right side shows correlations of animals with CMS. For statistical significance, Bonferroni correction was calculated and the p-value was adjusted for multiple comparisons. Indication: *, correlation is significant with p < 0.0036. (DOC 222 kb)

References

  1. 1.
    Temel Y, Hescham SA, Jahanshahi A, Janssen ML, Tan SK, van Overbeeke JJ, et al. Neuromodulation in psychiatric disorders. Int Rev Neurobiol. 2012;107:283–314. doi: 10.1016/B978-0-12-404706-8.00015-2.CrossRefPubMedGoogle Scholar
  2. 2.
    Temel Y, Lim LW. Neurosurgical treatments of depression. Curr Top Behav Neurosci. 2013;14:327–39. doi: 10.1007/7854_2012_222.CrossRefPubMedGoogle Scholar
  3. 3.
    Lim LW, Tan SK, Groenewegen HJ, Temel Y. Electrical brain stimulation in depression: which target(s)? Biol Psychiatry. 2011, 69:e5-6; author reply e7-8. doi  10.1016/j.biopsych.2010.09.056.
  4. 4.
    Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005;45:651–60. doi: 10.1016/j.neuron.2005.02.014.CrossRefPubMedGoogle Scholar
  5. 5.
    Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al. Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms. Transl Psychiatry. 2015;5:e535. doi: 10.1038/tp.2015.24.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Liu A, Jain N, Vyas A, Lim LW. Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats. Elife. 2015, 4. doi  10.7554/eLife.04803.
  7. 7.
    Lim LW, Janssen ML, Kocabicak E, Temel Y. The antidepressant effects of ventromedial prefrontal cortex stimulation is associated with neural activation in the medial part of the subthalamic nucleus. Behav Brain Res. 2015;279:17–21. doi: 10.1016/j.bbr.2014.11.008.CrossRefPubMedGoogle Scholar
  8. 8.
    Schlaepfer TE, Bewernick BH, Kayser S, Hurlemann R, Coenen VA. Deep brain stimulation of the human reward system for major depression--rationale, outcomes and outlook. Neuropsychopharmacology. 2014;39:1303–14. doi: 10.1038/npp.2014.28.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Holtzheimer 3rd PE, Mayberg HS. Deep brain stimulation for treatment-resistant depression. Am J Psychiatry. 2010;167:1437–44. doi: 10.1176/appi.ajp.2010.10010141.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008;64:461–7. doi: 10.1016/j.biopsych.2008.05.034.CrossRefPubMedGoogle Scholar
  11. 11.
    Holtzheimer PE, Kelley ME, Gross RE, Filkowski MM, Garlow SJ, Barrocas A, et al. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry. 2012;69:150–8. doi: 10.1001/archgenpsychiatry.2011.1456.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Jimenez F, Velasco F, Salin-Pascual R, Hernandez JA, Velasco M, Criales JL, Nicolini H. A patient with a resistant major depression disorder treated with deep brain stimulation in the inferior thalamic peduncle. Neurosurgery. 2005, 57:585-93; discussion -93.Google Scholar
  13. 13.
    Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, et al. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology. 2008;33:368–77. doi: 10.1038/sj.npp.1301408.CrossRefPubMedGoogle Scholar
  14. 14.
    Bewernick BH, Hurlemann R, Matusch A, Kayser S, Grubert C, Hadrysiewicz B, et al. Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression. Biol Psychiatry. 2010;67:110–6. doi: 10.1016/j.biopsych.2009.09.013.CrossRefPubMedGoogle Scholar
  15. 15.
    Bewernick BH, Kayser S, Sturm V, Schlaepfer TE. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology. 2012;37:1975–85. doi: 10.1038/npp.2012.44.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Malone Jr DA, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, et al. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009;65:267–75. doi: 10.1016/j.biopsych.2008.08.029.CrossRefPubMedGoogle Scholar
  17. 17.
    Dougherty DD, Rezai AR, Carpenter LL, Howland RH, Bhati MT, O’Reardon JP, et al. A randomized sham-controlled trial of deep brain stimulation of the ventral capsule/ventral striatum for chronic treatment-resistant depression. Biol Psychiatry. 2015;78:240–8. doi: 10.1016/j.biopsych.2014.11.023.CrossRefPubMedGoogle Scholar
  18. 18.
    Sartorius A, Kiening KL, Kirsch P, von Gall CC, Haberkorn U, Unterberg AW, et al. Remission of major depression under deep brain stimulation of the lateral habenula in a therapy-refractory patient. Biol Psychiatry. 2010;67:e9–e11. doi: 10.1016/j.biopsych.2009.08.027.CrossRefPubMedGoogle Scholar
  19. 19.
    Schlaepfer TE, Bewernick BH, Kayser S, Madler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013;73:1204–12. doi: 10.1016/j.biopsych.2013.01.034.CrossRefPubMedGoogle Scholar
  20. 20.
    Temel Y, Tan S, Vlamings R, Sesia T, Lim LW, Lardeux S, Visser-Vandewalle V, Baunez C. Cognitive and limbic effects of deep brain stimulation in preclinical studies. Front Biosci 2009;14(5):1891–1901. doi:  10.2741/3349
  21. 21.
    Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006;129:290–2. doi: 10.1093/brain/awh729.CrossRefPubMedGoogle Scholar
  22. 22.
    Schmahmann JD. From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp. 1996, 4:174-98. doi  10.1002/(SICI)1097-0193(1996)4:3&lt;174::AID-HBM3&gt;3.0.CO;2-0  10.1002/(SICI)1097-0193(1996)4:3<174::AID-HBM3>3.0.CO;2-0.
  23. 23.
    Moers-Hornikx VM, Sesia T, Basar K, Lim LW, Hoogland G, Steinbusch HW, et al. Cerebellar nuclei are involved in impulsive behaviour. Behav Brain Res. 2009;203:256–63. doi: 10.1016/j.bbr.2009.05.011.CrossRefPubMedGoogle Scholar
  24. 24.
    Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex. 2010;46:831–44. doi: 10.1016/j.cortex.2009.11.008.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Moers-Hornikx VM, Vles JS, Lim LW, Ayyildiz M, Kaplan S, Gavilanes AW, et al. Periaqueductal grey stimulation induced panic-like behaviour is accompanied by deactivation of the deep cerebellar nuclei. Cerebellum. 2011;10:61–9. doi: 10.1007/s12311-010-0228-z.CrossRefPubMedGoogle Scholar
  26. 26.
    Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121(Pt 4):561–79.CrossRefPubMedGoogle Scholar
  27. 27.
    Grieve SM, Korgaonkar MS, Koslow SH, Gordon E, Williams LM. Widespread reductions in gray matter volume in depression. Neuroimage Clin. 2013;3:332–9. doi: 10.1016/j.nicl.2013.08.016.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Liang MJ, Zhou Q, Yang KR, Yang XL, Fang J, Chen WL, et al. Identify changes of brain regional homogeneity in bipolar disorder and unipolar depression using resting-state FMRI. PLoS One. 2013;8:e79999. doi: 10.1371/journal.pone.0079999.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Guo W, Liu F, Liu J, Yu L, Zhang Z, Zhang J, et al. Is there a cerebellar compensatory effort in first-episode, treatment-naive major depressive disorder at rest? Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:13–8. doi: 10.1016/j.pnpbp.2013.06.009.CrossRefPubMedGoogle Scholar
  30. 30.
    Jiang WH, Yuan YG, Zhou H, Bai F, You JY, Zhang ZJ. Abnormally altered patterns of whole brain functional connectivity network of posterior cingulate cortex in remitted geriatric depression: a longitudinal study. CNS Neurosci Ther. 2014;20:772–7. doi: 10.1111/cns.12250.CrossRefPubMedGoogle Scholar
  31. 31.
    Frank B, Andrzejewski K, Goricke S, Wondzinski E, Siebler M, Wild B, et al. Humor, laughter, and the cerebellum: insights from patients with acute cerebellar stroke. Cerebellum. 2013;12:802–11. doi: 10.1007/s12311-013-0488-5.CrossRefPubMedGoogle Scholar
  32. 32.
    Akil H, Statham PF, Gotz M, Bramley P, Whittle IR. Adult cerebellar mutism and cognitive-affective syndrome caused by cystic hemangioblastoma. Acta Neurochir (Wien). 2006;148:597–8. doi: 10.1007/s00701-005-0646-8.CrossRefGoogle Scholar
  33. 33.
    Diaconescu AO, Kramer E, Hermann C, Ma Y, Dhawan V, Chaly T, et al. Distinct functional networks associated with improvement of affective symptoms and cognitive function during citalopram treatment in geriatric depression. Hum Brain Mapp. 2011;32:1677–91. doi: 10.1002/hbm.21135.CrossRefPubMedGoogle Scholar
  34. 34.
    Zeng LL, Liu L, Liu Y, Shen H, Li Y, Hu D. Antidepressant treatment normalizes white matter volume in patients with major depression. PLoS One. 2012;7:e44248. doi: 10.1371/journal.pone.0044248.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Chiu R, Boyle WJ, Meek J, Smeal T, Hunter T, Karin M. The c-Fos protein interacts with c-Jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 1988;54:541–52.CrossRefPubMedGoogle Scholar
  36. 36.
    Hestermann D, Temel Y, Blokland A, Lim LW. Acute serotonergic treatment changes the relation between anxiety and HPA-axis functioning and periaqueductal gray activation. Behav Brain Res 2014, 273:155-65. doi  10.1016/j.bbr.2014.07.003.
  37. 37.
    Lim LW, Blokland A, van Duinen M, Visser-Vandewalle V, Tan S, Vlamings R, Janssen M, Jahanshahi A, Aziz-Mohammadi M, Steinbusch HW, Schruers K, Temel Y. Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats. Behav Brain Res 2011, 218:301-7. doi  10.1016/j.bbr.2010.12.026.
  38. 38.
    Lim LW, Temel Y, Visser-Vandewalle V, Blokland A, Steinbusch H. Fos immunoreactivity in the rat forebrain induced by electrical stimulation of the dorsolateral periaqueductal gray matter. J Chem Neuroanat. 2009;38:83–96. doi: 10.1016/j.jchemneu.2009.06.011.CrossRefPubMedGoogle Scholar
  39. 39.
    Temel Y, Blokland A, Lim LW. Deactivation of the parvalbumin-positive interneurons in the hippocampus after fear-like behaviour following electrical stimulation of the dorsolateral periaqueductal gray of rats. Behav Brain Res. 2012;233:322–5. doi: 10.1016/j.bbr.2012.05.029.CrossRefPubMedGoogle Scholar
  40. 40.
    Lim LW, Temel Y, Sesia T, Vlamings R, Visser-Vandewalle V, Steinbusch HW and Blokland A. Buspirone induced acute and chronic changes of neural activation in the periaqueductal gray of rats. Neuroscience. 2008, 155:164-73. doi  10.1016/j.neuroscience.2008.05.038.
  41. 41.
    Lim LW, Blokland A, Tan S, Vlamings R, Sesia T, Aziz-Mohammadi M, Visser-Vandewalle V, Steinbusch HW, Schruers K, Temel Y. Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray. Exp Neurol. 2010, 226:293-300. doi  10.1016/j.expneurol.2010.08.035.
  42. 42.
    Tan S, Vlamings R, Lim L, Sesia T, Janssen ML, Steinbusch HW, Visser-Vandewalle V, Temel Y. Experimental deep brain stimulation in animal models. Neurosurgery. 2010, 67:1073-9; discussion80. doi  10.1227/NEU.0b013e3181ee3580.
  43. 43.
    Paxinos G, Watson C. The rat brain in stereotaxic coordinates. 6th ed. China: Academic Press of Elsevier; 2007.Google Scholar
  44. 44.
    Moers-Hornikx VMP, Vles JSH, Hemmes RJM, Lim LW, Hoogland G, Steinbusch HWM, et al. c-Fos expression in the deep cerebellar nuclei in a rat model of conditioned fear. J Exp Clin Med. 2012;29:201–7. doi: 10.5835/jecm.omu.29.03.007.CrossRefGoogle Scholar
  45. 45.
    Sullivan RM, Dufresne MM, Waldron J. Lateralized sex differences in stress-induced dopamine release in the rat. Neuroreport. 2009;20:229–32. doi: 10.1097/WNR.0b013e3283196b3e.CrossRefPubMedGoogle Scholar
  46. 46.
    Weathington JM, Puhy C, Hamki A, Strahan JA, Cooke BM. Sexually dimorphic patterns of neural activity in response to juvenile social subjugation. Behav Brain Res. 2013;256:464–71. doi: 10.1016/j.bbr.2013.08.042.CrossRefPubMedGoogle Scholar
  47. 47.
    Schulz KM, Andrud KM, Burke MB, Pearson JN, Kreisler AD, Stevens KE, et al. The effects of prenatal stress on alpha4 beta2 and alpha7 hippocampal nicotinic acetylcholine receptor levels in adult offspring. Dev Neurobiol. 2013;73:806–14. doi: 10.1002/dneu.22097.PubMedPubMedCentralGoogle Scholar
  48. 48.
    Soza Ried AM, Aviles M. Asymmetries of vestibular dysfunction in major depression. Neuroscience. 2007;144:128–34. doi: 10.1016/j.neuroscience.2006.09.023.CrossRefPubMedGoogle Scholar
  49. 49.
    Kilts CD, Kelsey JE, Knight B, Ely TD, Bowman FD, Gross RE, et al. The neural correlates of social anxiety disorder and response to pharmacotherapy. Neuropsychopharmacology. 2006;31:2243–53. doi: 10.1038/sj.npp.1301053.CrossRefPubMedGoogle Scholar
  50. 50.
    Warwick JM, Carey P, Jordaan GP, Dupont P, Stein DJ. Resting brain perfusion in social anxiety disorder: a voxel-wise whole brain comparison with healthy control subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1251–6. doi: 10.1016/j.pnpbp.2008.03.017.CrossRefPubMedGoogle Scholar
  51. 51.
    Bremner JD, Narayan M, Staib LH, Southwick SM, McGlashan T, Charney DS. Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder. Am J Psychiatry. 1999;156:1787–95. doi: 10.1176/ajp.156.11.1787.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Bonne O, Gilboa A, Louzoun Y, Brandes D, Yona I, Lester H, et al. Resting regional cerebral perfusion in recent posttraumatic stress disorder. Biol Psychiatry. 2003;54:1077–86.CrossRefPubMedGoogle Scholar
  53. 53.
    Blair K, Shaywitz J, Smith BW, Rhodes R, Geraci M, Jones M, et al. Response to emotional expressions in generalized social phobia and generalized anxiety disorder: evidence for separate disorders. Am J Psychiatry. 2008;165:1193–202. doi: 10.1176/appi.ajp.2008.07071060.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Allen G, McColl R, Barnard H, Ringe WK, Fleckenstein J, Cullum CM. Magnetic resonance imaging of cerebellar-prefrontal and cerebellar-parietal functional connectivity. Neuroimage. 2005;28:39–48. doi: 10.1016/j.neuroimage.2005.06.013.CrossRefPubMedGoogle Scholar
  55. 55.
    Kamali A, Kramer LA, Frye RE, Butler IJ, Hasan KM. Diffusion tensor tractography of the human brain cortico-ponto-cerebellar pathways: a quantitative preliminary study. J Magn Reson Imaging. 2010;32:809–17. doi: 10.1002/jmri.22330.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Leergaard TB, Bjaalie JG. Topography of the complete corticopontine projection: from experiments to principal Maps. Front Neurosci. 2007;1:211–23. doi: 10.3389/neuro.01.1.1.016.2007.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Rogers TD, Dickson PE, Heck DH, Goldowitz D, Mittleman G, Blaha CD. Connecting the dots of the cerebro-cerebellar role in cognitive function: neuronal pathways for cerebellar modulation of dopamine release in the prefrontal cortex. Synapse. 2011;65:1204–12. doi: 10.1002/syn.20960.CrossRefPubMedGoogle Scholar
  58. 58.
    Lalonde R, Strazielle C. The effects of cerebellar damage on maze learning in animals. Cerebellum. 2003;2:300–9. doi: 10.1080/14734220310017456.CrossRefPubMedGoogle Scholar
  59. 59.
    Dum RP, Li C, Strick PL. Motor and nonmotor domains in the monkey dentate. Ann N Y Acad Sci. 2002;978:289–301.CrossRefPubMedGoogle Scholar
  60. 60.
    Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol. 2003;89:634–9. doi: 10.1152/jn.00626.2002.CrossRefPubMedGoogle Scholar
  61. 61.
    Schmahmann JD. The role of the cerebellum in cognition and emotion: personal reflections since 1982 on the dysmetria of thought hypothesis, and its historical evolution from theory to therapy. Neuropsychol Rev. 1982;2010(20):236–60. doi: 10.1007/s11065-010-9142-x.Google Scholar
  62. 62.
    Nashold Jr BS, Slaughter DG. Effects of stimulating or destroying the deep cerebellar regions in man. J Neurosurg. 1969;31:172–86. doi: 10.3171/jns.1969.31.2.0172.CrossRefPubMedGoogle Scholar
  63. 63.
    Bauer DJ, Kerr AL, Swain RA. Cerebellar dentate nuclei lesions reduce motivation in appetitive operant conditioning and open field exploration. Neurobiol Learn Mem. 2011;95:166–75. doi: 10.1016/j.nlm.2010.12.009.CrossRefPubMedGoogle Scholar
  64. 64.
    Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum—insights from the clinic. Cerebellum. 2007;6:254–67. doi: 10.1080/14734220701490995.CrossRefPubMedGoogle Scholar
  65. 65.
    Schmahmann JD, Pandya DN, Wang R, Dai G, D’Arceuil HE, de Crespigny AJ, et al. Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain. 2007;130:630–53. doi: 10.1093/brain/awl359.CrossRefPubMedGoogle Scholar
  66. 66.
    Rapkin AJ, Berman SM, Mandelkern MA, Silverman DH, Morgan M, London ED. Neuroimaging evidence of cerebellar involvement in premenstrual dysphoric disorder. Biol Psychiatry. 2011;69:374–80. doi: 10.1016/j.biopsych.2010.09.029.CrossRefPubMedGoogle Scholar
  67. 67.
    Rijkers K, Moers-Hornikx VM, Hemmes RJ, Aalbers MW, Temel Y, Vles JS, et al. Sustained reduction of cerebellar activity in experimental epilepsy. Biomed Res Int. 2015;2015:718591. doi: 10.1155/2015/718591.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Nakayama K, Kiyosue K, Taguchi T. Diminished neuronal activity increases neuron-neuron connectivity underlying silent synapse formation and the rapid conversion of silent to functional synapses. J Neurosci. 2005;25:4040–51. doi: 10.1523/JNEUROSCI.4115-04.2005.CrossRefPubMedGoogle Scholar
  69. 69.
    Burrone J, O’Byrne M, Murthy VN. Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature. 2002;420:414–8. doi: 10.1038/nature01242.CrossRefPubMedGoogle Scholar
  70. 70.
    Lu X, Miyachi S, Takada M. Anatomical evidence for the involvement of medial cerebellar output from the interpositus nuclei in cognitive functions. Proc Natl Acad Sci U S A. 2012;109:18980–4. doi: 10.1073/pnas.1211168109.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Wu GY, Yao J, Fan ZL, Zhang LQ, Li X, Zhao CD, et al. Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs. Acta Pharmacol Sin. 2012;33:717–27. doi: 10.1038/aps.2012.32.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Wang YJ, Chen H, Hu C, Ke XF, Yang L, Xiong Y, et al. Baseline theta activities in medial prefrontal cortex and deep cerebellar nuclei are associated with the extinction of trace conditioned eyeblink responses in guinea pigs. Behav Brain Res. 2014;275:72–83. doi: 10.1016/j.bbr.2014.08.059.CrossRefPubMedGoogle Scholar
  73. 73.
    Carleton SC, Carpenter MB. Afferent and efferent connections of the medial, inferior and lateral vestibular nuclei in the cat and monkey. Brain Res. 1983;278:29–51.CrossRefPubMedGoogle Scholar
  74. 74.
    Godemann F, Linden M, Neu P, Heipp E, Dorr P. A prospective study on the course of anxiety after vestibular neuronitis. J Psychosom Res. 2004;56:351–4. doi: 10.1016/S0022-3999(03)00079-5.CrossRefPubMedGoogle Scholar
  75. 75.
    Godemann F, Siefert K, Hantschke-Bruggemann M, Neu P, Seidl R, Strohle A. What accounts for vertigo one year after neuritis vestibularis—anxiety or a dysfunctional vestibular organ? J Psychiatr Res. 2005;39:529–34. doi: 10.1016/j.jpsychires.2004.12.006.CrossRefPubMedGoogle Scholar
  76. 76.
    Kalueff AV, Ishikawa K, Griffith AJ. Anxiety and otovestibular disorders: linking behavioral phenotypes in men and mice. Behav Brain Res. 2008;186:1–11. doi: 10.1016/j.bbr.2007.07.032.CrossRefPubMedGoogle Scholar
  77. 77.
    Smith PF, Zheng Y, Horii A, Darlington CL. Does vestibular damage cause cognitive dysfunction in humans? J Vestib Res. 2005;15:1–9.PubMedGoogle Scholar
  78. 78.
    Halberstadt AL, Balaban CD. Organization of projections from the raphe nuclei to the vestibular nuclei in rats. Neuroscience. 2003;120:573–94.CrossRefPubMedGoogle Scholar
  79. 79.
    Balaban CD. Neural substrates linking balance control and anxiety. Physiol Behav. 2002;77:469–75.CrossRefPubMedGoogle Scholar
  80. 80.
    Gray JA, McNaughton N. The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septohippocampal System, 2nd Edition..Oxford University Press 2000.Google Scholar
  81. 81.
    Halberstadt AL, Balaban CD. Anterograde tracing of projections from the dorsal raphe nucleus to the vestibular nuclei. Neuroscience. 2006;143:641–54. doi: 10.1016/j.neuroscience.2006.08.013.CrossRefPubMedGoogle Scholar
  82. 82.
    Halberstadt AL, Balaban CD. Serotonergic and nonserotonergic neurons in the dorsal raphe nucleus send collateralized projections to both the vestibular nuclei and the central amygdaloid nucleus. Neuroscience. 2006;140:1067–77. doi: 10.1016/j.neuroscience.2006.02.053.CrossRefPubMedGoogle Scholar
  83. 83.
    Wulff P, Schonewille M, Renzi M, Viltono L, Sassoe-Pognetto M, Badura A, et al. Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat Neurosci. 2009;12:1042–9. doi: 10.1038/nn.2348.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Verduzco-Flores S. Stochastic synchronization in purkinje cells with feedforward inhibition could be studied with equivalent phase-response curves. J Math Neurosci. 2015;5:25. doi: 10.1186/s13408-015-0025-6.CrossRefPubMedGoogle Scholar
  85. 85.
    Chen H, Wang YJ, Yang L, Sui JF, Hu ZA, Hu B. Theta synchronization between medial prefrontal cortex and cerebellum is associated with adaptive performance of associative learning behavior. Sci Rep. 2016;6:20960. doi: 10.1038/srep20960.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of BiologyUniversity of GironaGironaSpain
  2. 2.Departments of Neuroscience and NeurosurgeryMaastricht UniversityMaastrichtThe Netherlands
  3. 3.School of Biomedical Sciences, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  4. 4.Department of Biological SciencesSunway UniversityBandar SunwayMalaysia

Personalised recommendations