c-Fos expression in the deep cerebellar nuclei in a rat model of conditioned fear

In contrast to what was previously believed, there is increasing evidence that the cerebellum is involved in emotional and cognitive behaviour. Preclinical and clinical research points towards a role of the cerebellum in impulsivity and panic. Deep brain stimulation (DBS) of the dorsolateral periaqueductal gray (dlPAG) in rats has proved to elicit escape behaviour directly, but can also be used for conditioning of context-dependant fear responses. We used this model to study the activation in the deep cerebellar nuclei (DCbN) after conditioned fear. For this purpose, we performed c-Fos immunohistochemistry in the DCbN. We found no statistically significant difference in c-Fos expression in the DCbN between the subgroups in this animal model. We hypothesize that the lack of a significant difference in activation of the DCbN may be related to fear consolidation which takes place after dlPAG stimulation, after which retrieval of behaviour, whether adequate or inadequate, does not lead to a different activation of the DCbN. On the other hand the effect of conditioned fear may be smaller than the effect of panic behaviour elicited by DBS, requiring a larger study population.

___

  • Allen, G., McColl, R., Barnard, H., Ringe, W.K., Fleckenstein, J., Cullum, C.M., 2005. Magnetic resonance imaging of cerebellar-prefrontal and cerebellar-parietal functional connectivity. NeuroImage. 28, 39-48.
  • Assié, M.B., Lomenech, H., Ravailhe, V., Faucillon, V., Newman-Tancredi, A., 2006. Rapid desensitization of somatodendritic 5-HT1A receptors by chronic administration of the high-efficacy 5-HT1A agonist, F13714: A microdialysis study in the rat. Br. J. Pharmacol. 149, 170-178.
  • Baillieux, H., De Smet, H.J., Dobbeleir, A., Paquier, P.F., De Deyn, P.P., Mariën, P., 2010. Cognitive and affective disturbances following focal cerebellar damage in adults: A neuropsychological and SPECT study. Cortex. 46, 869-879.
  • Baillieux, H., De Smet, H.J., Paquier, P.F., De Deyn, P.P., Mariën, P., 2008. Cerebellar neurocognition: Insights into the bottom of the brain. Clin. Neurol. Neurosur. 110, 763-773.
  • Bondi, C.O., Rodriguez, G., Gould, G.G., Frazer, A., Morilak, D.A., 2008. Chronic unpredictable stress induces a cognitive deficit and anxietylike behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacol. 33, 320-331.
  • Brodal, P., 1978. The corticopontine projection in the rhesus monkey. Origin and principles of organization. Brain. 101, 251-283.
  • Brodal, P., Bjaalie, J.G., Aas, J.E., 1991. Organization of cingulo-ponto-cerebellar connections in the cat. Anat. Embryol. 184, 245-254.
  • Burghardt, N.S., Sullivan, G.M., McEwen, B.S., Gorman, J.M., LeDoux, J.E., 2004. The selective serotonin reuptake inhibitor citalopram increases fear after acute treatment but reduces fear with chronic treatment: A comparison with tianeptine. Biol. Psychiat. 55, 1171-1178.
  • Cantalupo, C., Hopkins, W., 2010. The cerebellum and its contribution to complex tasks in higher primates: A comparative perspective. Cortex. 46, 821-830.
  • Cavdar, S., Onat, F.Y., Yananli, H.R., Sehirli, U.S., Tulay, C., Saka, E., Gürdal, E., 2002. Cerebellar connections to the rostral reticular nucleus of the thalamus in the rat. J. Anat. 201, 485-491.
  • de Ribaupierre, S., Ryser, C., Villemure, J.G., Clarke, S., 2008. Cerebellar lesions: Is there a lateralisation effect on memory deficits? Acta Neurochir. 150, 545-550.
  • Desbonnet, L., Temel, Y., Visser-Vandewalle, V., Blokland, A., Hornikx, V., Steinbusch, H.W., 2004. Premature responding following bilateral stimulation of the rat subthalamic nucleus is amplitude and frequency dependent. Brain Res. 1008, 198-204.
  • Dietrichs, E., Haines, D.E., Røste, G.K., Røste, L.S., 1994. Hypothalamocerebellar and cerebellohypothalamic projections-circuits for regulating nonsomatic cerebellar activity? Histol. Histopathol. 9, 603-614.
  • Duan, X.Q., Wu, S.L., Li, T., Liang, J.C., Qiou, J.Y., Rao, Z.R., Ju, G., 1999. Expression and significance of three types of Fos-immunoreactive cells after gamma knife irradiation of the forebrain in the rat. Neurosci. Res. 33, 99-104.
  • Fine, E.J., Ionita, C.C., Lohr, L., 2002. The history of the development of the cerebellar examination. Semin. Neurol. 22, 375-384.
  • Glickstein, M., Strata, P., Voogd, J., 2009. Cerebellum: History. Neuroscience. 162, 549-559.
  • Leiner, H.C., Leiner, A.L., Dow, R.S., 1986. Does the cerebellum contribute to mental skills? Behav. Neurosci. 100, 443-454.
  • Leiner, H.C., Leiner, A.L., Dow, R.S., 1993. Cognitive and language functions of the human cerebellum. Trends Neurosci. 16, 444-447.
  • Lim, L.W., Blokland, A., Tan, S., Vlamings, R., Sesia, T., Aziz-Mohammadi, M., Visser-Vandewalle, V., Steinbusch, H.W., Schruers, K., Temel, Y., 2010. Attenuation of fear-like response by escitalopram treatment after electrical stimulation of the midbrain dorsolateral periaqueductal gray. Exp. Neurol. 226, 293-300.
  • Lim, L.W., Blokland, A., Visser-Vandewalle, V., Vlamings, R., Sesia, T., Steinbusch, H., Schruers, K., Griez, E., Temel, Y., 2008. High-frequency stimulation of the dorsolateral periaqueductal gray and ventromedial hypothalamus fails to inhibit panic-like behaviour. Behav. Brain Res. 193, 197-203.
  • Lim, L.W., Temel, Y., Visser-Vandewalle, V., Steinbusch, H., Schruers, K., Hameleers, R., Esquivel, G., Griez, E., Blokland, A., 2008. Effect of buspirone on the behavioral regulation of rats in low versus high anxiety conditions. Arzneimittelforschung. 58, 269-276.
  • Lino-de-Oliveira, C., de Oliveira, R.M., Pádua Carobrez, A., de Lima, T.C., del Bel, E.A., Guimarães, F.S., 2006. Antidepressant treatment reduces Fos-like immunoreactivity induced by swim stress in different columns of the periaqueductal gray matter. Brain Res. Bull. 70, 414421.
  • Manto, M., 2008. The cerebellum, cerebellar disorders, and cerebellar research--two centuries of discoveries. Cerebellum. 7, 505-516.
  • Marien, P., Engelborghs, S., De Deyn, P.P., 2001. Cerebellar neurocognition: A new avenue. Acta Neurol. Belg. 101, 96-109.
  • Middleton,, F.A., Strick, P.L., 2000. Basal ganglia and cerebellar loops: Motor and cognitive circuits. Brain Res. Rev. 31, 236-250.
  • Middleton, F.A., Strick, P.L., 2001. Cerebellar projections to the prefrontal cortex of the primate. J. Neurosci. 21, 700-712.
  • Moers-Hornikx, V.M., Sesia, T., Basar, K., Lim, L.W., Hoogland, G., Steinbusch, H.W., Gavilanes, D.A., Temel, Y., Vles, J.S., 2009. Cerebellar nuclei are involved in impulsive behaviour. Behav. Brain Res. 203, 256-263.
  • Moers-Hornikx, V.M., Vles, J.S., Lim, L.W., Ayyildiz, M., Kaplan, S., Gavilanes, A.W., Hoogland, G., Steinbusch, H.W., Temel, Y., 2011. Periaqueductal grey stimulation induced panic-like behaviour is accompanied by deactivation of the deep cerebellar nuclei. Cerebellum. 10, 61-69.
  • Moers-Hornikx, V.M., Vles, J.S., Tan, S.K., Cox, K., Hoogland, G., Steinbusch, W.M., Temel, Y., 2011. Cerebellar nuclei are activated by highfrequency stimulation of the subthalamic nucleus. Neurosci. Lett. 496, 111-115.
  • Paulesu, E., Frith, C.D., Frackowiak, R.S.,1993. The neural correlates of the verbal component of working memory. Nature. 362, 342-345.
  • Pearce, J.M., 2009. Marie-Jean-Pierre Flourens (1794-1867) and cortical localization. Eur. Neurol. 61, 311-314.
  • Sacchetti, B., Scelfo, B., Strata, P., 2005. The cerebellum: synaptic changes and fear conditioning. Neuroscientist. 11, 217-227.
  • Sacchetti, B., Scelfo, B., Strata, P., 2009. Cerebellum and emotional behavior. Neuroscience. 162, 756-762.
  • Sato, H,, Skelin, I., Debonnel, G., Diksic, M., 2008. Chronic buspirone treatment normalizes open field behavior in olfactory bulbectomized rats: Assessment with a quantitative autoradiographic evaluation of the 5-HT1A binding sites. Brain Res. Bull. 75, 545-555.
  • Schmahmann, J.D., 1996. From movement to thought: Anatomic substrates of the cerebellar contribution to cognitive processing. Hum. Brain Mapp. 4, 174-198.
  • Schmahmann, J.D., 2010. 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. 20, 236-260.
  • Schmahmann, J.D., Pandya, D.N., 1991. Projections to the basis pontis from the superior temporal sulcus and superior temporal region in the rhesus monkey. J. Comp. Neurol. 308, 224-248.
  • Schmahmann, J.D., Pandya, D.N., 1993. Prelunate, occipitotemporal, and parahippocampal projections to the basis pontis in rhesus monkey. J. Comp. Neurol. 337, 94-112.
  • Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain. 121, 561-579.
  • Smith, M.A., Banerjee, S., Gold, P.W., Glowa, J., 1992. Induction of c-fos mRNA in rat brain by conditioned and unconditioned stressors. Brain Res. 578, 135-141.
  • Snider, R.S., Maiti, A., 1976. Cerebellar contributions to the Papez circuit. J. Neurosci. Res. 2, 133-146.
  • Tan, S.Kh., Vlamings, R., Lim, L., Sesia, T., Janssen, M.L., Steinbusch, H.W., Visser-Vandewalle, V., Temel, Y., 2010. Experimental deep brain stimulation in animal models. Neurosurgery. 67, 1073-1079.
  • Temel, Y., Boothman, L.J., Blokland, A., Magill, P.J., Steinbusch, H.W., Visser-Vandewalle, V., Sharp, T., 2007. Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. P. Natl. Acad. Sci. USA. 104, 17087-17092.
  • Turner, B.M., Paradiso, S., Marvel, C.L., Pierson, R., Boles Ponto, L.L., Hichwa, R.D., Robinson, R.G., 2007. The cerebellum and emotional experience. Neuropsychologia. 45, 1331-1341.
  • Watson, G.P.C., 1998. The rat brain in stereotaxic coordinates, Academic press. 61-68
  • Wells, E.M., Walsh, K.S., Khademian, Z.P., Keating, R.F., Packer, R.J., 2008. The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder. Dev. Disabil. Res. Rev. 14, 221-228.
  • Yamamoto, T., Yoshida, K., Yoshikawa, H., Kishimoto, Y., Oka, H.,1992. The medial dorsal nucleus is one of the thalamic relays of the cerebellocerebral responses to the frontal association cortex in the monkey: Horseradish peroxidase and fluorescent dye double staining study. Brain Res. 579, 315-320.
Journal of Experimental and Clinical Medicine-Cover
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1980
  • Yayıncı: Ondokuz mayıs Üniversitesi Tıp Fakültesi