Behavior Genetics

, Volume 34, Issue 3, pp 319–324

Spatial Memory of Heterozygous Staggerer (Rora+/Rorasg) Versus Normal (Rora+/Rora+) Mice During Aging

  • J. Caston
  • C. Chianale
  • J. Mariani


Heterozygous staggerer mice (Rora+/Rorasg) and control mice (Rora+/Rora+) of the same C57BL/6J strain background were tested in a spontaneous alternation task at 3 to 24 months old. The results demonstrated a decrement in long-term working memory as early as 6 months in Rora+/Rora+ mice and at 3 months in Rora+/Rorasg mice. Previous studies showed that in both cases, neuronal number in the cerebellar cortex was normal (Doulazmi et al. [1999]). This suggests that age-dependent decrease in long-term working memory would be due to fine structural or biochemical changes preceding neuronal death in the cerebellum. Such subtle changes would occur more precociously in Rora+/Rorasg than in Rora+/Rora+ mice. Also, short-term working memory was preserved in Rora+/Rora+ mice as old as 24 months, but was impaired in 6-month-old Rora+/Rorasg mice.

Aging spontaneous alternation spatial memory cerebellum staggerer mutant mouse 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bakalian, A., Corman, B., Delhaye-Bouchaud, N., and Mariani, J. (1991). Stability of the number of Purkinje cells during aging in rats. Neurobiol. Aging 12:425-430.Google Scholar
  2. Bakalian, A., Kopmels, B., Messer, A., Fradelizi, D., Delhaye-Bouchaud, N., Wollman, E., and Mariani, J. (1992). Peripheral macrophages abnormalities in mutant mice with spino-cerebellar degeneration. Res. Immunol. 143:129-139.Google Scholar
  3. Blatt, G. J., and Eisenman, L. M. (1985). A qualitative and quantitative light microscopic study of the inferior olivary complex in the adult staggerer mutant mouse. J. Neurogenet. 2:51-66.Google Scholar
  4. Caddy, K. W. T., and Biscoe, T. J. (1979). Structural and quantitative studies on normal C3H and lurcher mutant mouse. Phil. Trans. R. Soc. Lond. 287:167-201.Google Scholar
  5. Caston, J., Delhaye-Bouchaud, N., and Mariani, J. (1996). Motor behavior of heterozygous staggerer mutant (+/sg) versus normal (+/+) mice during aging. Behav. Brain Res. 72:97-102.Google Scholar
  6. Caston, J., Lalonde, R., Delhaye-Bouchaud, N., and Mariani, J. (1998). The cerebellum and postural sensorimotor learning in mice and rats. Behav. Brain Res. 95:17-22.Google Scholar
  7. Caston, J., Vasseur, F., Delhaye-Bouchaud, N., and Mariani, J. (1997). Delayed spontaneous alternation in intact and cerebellectomized control and lurcher mutant mice: Differential role of cerebellar cortex and deep cerebellar nuclei. Behav. Neurosci. 111:214-218.Google Scholar
  8. Clark, G. A., McCormick, D. A., Lavond, D. G., and Thompson, R. F. (1984). Effects of lesion of cerebellar nuclei on conditioned behavioral and hippocampal neuronal responses. Brain Res. 291:125-136.Google Scholar
  9. Dahhaoui, M., Lannou, J., Stelz, T., Caston, J., and Guastavino, J. M. (1992a). Role of the cerebellum in spatial orientation in the rat. Behav. Neural Biol. 58:180-189.Google Scholar
  10. Dahhaoui, M., Stelz, T., and Caston, J. (1992b). Effects of lesion of the inferior olivary complex by 3-acetylpyridine on learning and memory in the rat. J. Comp. Physiol. A 171:657-664.Google Scholar
  11. Deiss, V., Dubois, M., Lalonde, R., and Strazielle, C. (2001). Cytochrome oxidase activity in the olfactory system of staggerer mutant mice. Brain Res. 910:126-133.Google Scholar
  12. Doulazmi, M., Frédéric, F., Lemaigre-Dubreuil, Y., Hadj-Sahraoui, N., Delhaye-Bouchaud, N., and Mariani, J. (1999). Cerebellar Purkinje cell loss during life span of the heterozygous staggerer mouse (Rora+/Rorasg) is gender-related. J. Comp. Neurol. 411:267-273.Google Scholar
  13. Eichenbaum, H., Stewart, C., and Morris, R. G. M. (1990). Hippocampal representation in spatial learning. J. Neurosci. 10:331-339.Google Scholar
  14. Freeman, J. S., Cody, F. W. J., O'Boyle, D. J., Crauford, D., Neary, D., and Snowden, J. S. (1996). Abnormalities of motor timing in Huntington's disease. Parkinsonism Rel. Disord. 2:81-93.Google Scholar
  15. Gandhi, C. C., Kellyl, R. M., Wiley, R. G., and Walsh, T. J. (2000). Impaired acquisition of a Morris water maze task following selective destruction of cerebellar Purkinje cells with OX7-saporin. Behav. Brain Res. 109:37-47.Google Scholar
  16. Goodlett, C. R., Hamre, K. M., and West, J. R. (1992). Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice. Behav. Brain Res. 47:129-141.Google Scholar
  17. Hadj-Sahraoui, N., Frédéric, F., Zanjani, H., Delhaye-Bouchaud, N., Herrup, K., and Mariani, J. (2001). Progressive atrophy of cerebellar Purkinje cell dendrites during aging of the heterozygous staggerer mouse (Rora+/Rorasg). Dev. Brain Res. 126:201-209.Google Scholar
  18. Hadj-Sahraoui, N., Frédéric, F., Zanjani, H., Herrup, K., Delhaye-Bouchaud, N., and Mariani, J. (1997). Purkinje cell loss in heterozygous staggerer mutant mice during aging. Dev. Brain Res. 98:1-8.Google Scholar
  19. Heath, R. G., Dempesy, C. W., Fontana, C. J., and Myers, W. A. (1978). Cerebellar stimulation: Effects on septal region, hippocampus, and amygdala of cats and rats. Biol. Psychiatr. 13:501-529.Google Scholar
  20. Herrup, K., and Mullen, R. J. (1979). Regional variation and absence of large neurons in the cerebellum of the staggerer mouse. Brain Res. 172:1-12.Google Scholar
  21. Hilber, P., Jouen, F., Delhaye-Bouchaud, N., Mariani, J., and Caston, J. (1998). Differential roles of cerebellar cortex and deep cerebellar nuclei in learning and retention of a spatial task: Studies in intact and cerebellectomized lurcher mutant mice. Behav. Genet. 28:299-308.Google Scholar
  22. Isseroff, A. (1979). Limited recovery of spontaneous alternation after extensive hippocampal damage: Evidence for a memory impairment. Exp. Neurol. 64:284-294.Google Scholar
  23. Ivry, R. V., and Keele, S. W. (1989). Timing functions of the cerebellum. J. Cogn. Neurosci. 1:136-152.Google Scholar
  24. Johnson, C. T., Olton, D. S., Gage, F. H., and Jenko, P. G. (1977). Damage to the hippocampus and hippocampal connections: Effects on DRL and spontaneous alternation. J. Comp. Physiol. Psychol. 91:508-522.Google Scholar
  25. Joyal, C. C., Meyer, C., Jacquart, G., Mahler, P., Caston, J., and Lalonde, R. (1996). Effects of midline and lateral cerebellar lesions on motor coordination and spatial orientation. Brain Res. 739:1-11.Google Scholar
  26. Keele, S. W., and Ivry, R. V. (1990). Does the cerebellum provide a common computation for drive tasks? A timing hypothesis. Ann. NY Acad. Sci. 608:179-211.Google Scholar
  27. Kopmels, B., Mariani, J., Delhaye-Bouchaud, N., Audibert, F., Fradelizi, D., and Wollman, E. (1992). Evidence for a hyperexcitability state of staggerer mutant mice macrophages. J. Neurochem. 58:192-199.Google Scholar
  28. Kopmels, B., Mariani, J., Taupin, V., Delhaye-Bouchaud, N., and Wollman, E. (1991). Differential IL-6 mRNA expression by stimulated peripheral macrophages of staggerer and lurcher cerebellar mutant mice. Eur. Cytokine Netw. 2:345-353.Google Scholar
  29. Kopmels, B., Wollman, E., Guastavino, J. M., Delhaye-Bouchaud, N., Fradelizi, D., and Mariani, J. (1990). Hyperexpression of IL-6 mRNA by in vitro activated peripheral macrophages from cerebellar mutant mice. J. Neurochem. 55:1980-1985.Google Scholar
  30. Lalonde, R. (1987). Exploration and spatial learning in staggerer mutant mice. J. Neurogenet. 4:285-292.Google Scholar
  31. Lalonde, R. (2002). The neurological basis of spontaneous alternation. Neuroscience Biobehav. Rev. 26:91-104.Google Scholar
  32. Lalonde, R., Filali, M., Bensoula, A. N., Monnier, C., and Guastavino, J. M. (1996). Spatial learning in a Z-maze by cerebellar mutant mice. Physiol. Behav. 59:83-86.Google Scholar
  33. Lalonde, R., Joyal, C. C., Côté, C., and Botez, M. I. (1993). Delayed spontaneous alternation in lurcher mutant mice. Psychobiology 21:139-141.Google Scholar
  34. Lalonde, R., Lamarre, Y., and Smith, A. M. (1988). Does the mutant mouse lurcher have deficits in spatially oriented behaviors? Brain Res. 455:24-30.Google Scholar
  35. Lalonde, R., Lamarre, Y., Smith, A. M., and Botez, M. I. (1986). Spontaneous alternation and habituation in lurcher mutant mice. Brain Res. 362:161-164.Google Scholar
  36. Le Marec, N., Dahhaoui, M., Stelz, T., Bakalian, A., Delhaye-Bouchaud, N., Caston, J., and Mariani, J. (1997). Effects of cerebellar granule cell depletion on spatial learning and memory and in an avoidance conditioning task: Studies in postnatally X-irradiated rats. Dev. Brain Res. 99:20-28.Google Scholar
  37. Meignin, C., Hilber, P., and Caston, J. (1999). Influence of stimulation of the olivocerebellar pathway by harmaline on spatial learning in the rat. Brain Res. 824:277-283.Google Scholar
  38. Michel, V., Monnier, Z., Guastavino, J. M., Propper, A., and Math, F. (2000). Functional alterations in the olfactory bulb of the staggerer mutant mouse. Neurosci. Lett. 280:1-4.Google Scholar
  39. Molinari, M., Grammaldo, L. G., and Petrosini, L. (1997). Cerebellar contribution to spatial event processing: Right/left discrimination abilities in rats. Eur. J. Neurosci. 9:1986-1992.Google Scholar
  40. Monnier, Z., Bahjaoui-Bouhaddi, M., Bride, J., Bride, M., Math, F., and Propper, A. (1999). Structural and immunohistological modifications in olfactory bulb of the staggerer mutant mouse. Biol. Cell 91:29-44.Google Scholar
  41. Nadel, L. (1991). The hippocampus and space revisited. Hippocampus 1:221-229.Google Scholar
  42. Newman, P. P., and Reza, H. (1979). Functional relationships between the hippocampus and the cerebellum: An electrophysiological study in the cat. J. Physiol. (Lond.) 287:405-426.Google Scholar
  43. O'Boyle, D. J., Freeman, J. S., and Cody, F. W. J. (1996). The accuracy and precision of timing of self-placed, repetitive movements in subjects with Parkinson's disease. Brain 119:51-70.Google Scholar
  44. O'Keefe, J. A. (1979). A review of hippocampal place cells. Progr. Neurobiol. 13:419-439.Google Scholar
  45. O'Keefe, J. A., and Nadel, L. (1978). The Hippocampus as a Cognitive Map. Oxford, England: Oxford University Press.Google Scholar
  46. O'Keefe, J. A., and Speakman, A. (1987). Single unit activity in the rat hippocampus during a spatial memory task. Exper. Brain Res. 68:1-27.Google Scholar
  47. Packard, M. G., and McGaugh, J. L. (1996). Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning. Neurobiol. Learn. Mem. 65:65-72.Google Scholar
  48. Roberts, W. W., Dember, W. N., and Brodwick, M. (1962). Alternation and exploration in rats with hippocampal lesions. J. Comp. Physiol. Psychol. 55:695-700.Google Scholar
  49. Shojaeian, H., Delhaye-Bouchaud, N., and Mariani, J. (1985). Decreased number of cells in the inferior olivary nucleus of the developing staggerer mouse. Brain Res. 353:141-146.Google Scholar
  50. Snider, R. S., and Maiti, A. (1976). Cerebellar contributions to the Papez circuit. J. Neurosci. Res. 2:133-146.Google Scholar
  51. Zanjani, H. S., Herrup, K., Guastavino, J. M., Delhaye-Bouchaud, N., and Mariani, J. (1994). Developmental studies of the inferior olivary nucleus in staggerer mutant mice. Dev. Brain Res. 82:18-28.Google Scholar
  52. Zanjani, H. S., Mariani, J., Delhaye-Bouchaud, N., and Herrup, K. (1992). Neuronal cell loss in heterozygous staggerer mutant mice: A model for genetic contribution to the aging process. Dev. Brain Res. 67:153-160.Google Scholar
  53. Zanjani, H. S., Mariani, J., and Herrup, K. (1990). Cell loss in the inferior olive of the staggerer mutant mouse is an indirect effect of the gene. J. Neurogenet. 6:229-241.Google Scholar

Copyright information

© Plenum Publishing Corporation 2004

Authors and Affiliations

  • J. Caston
    • 1
  • C. Chianale
    • 2
  • J. Mariani
    • 3
  1. 1.UPRES EA 1780, Laboratoire de Neurobiologie de l'Apprentissage, Faculté des SciencesUniversité de RouenFrance
  2. 2.Institut Gustave RoussyVillejuifFrance
  3. 3.Laboratoire Développement et Vieillissement du Système Nerveux, UMR7102 Neurobiologie des Processus AdaptatifsCNRS et Université Pierre et Marie CurieParisFrance

Personalised recommendations