An ultrastructural study of granule cell/Purkinje cell synapses in tottering (tg/tg), leaner (tg(la)/tg(la)) and compound heterozygous tottering/leaner (tg/tg(la)) mice

I. J. Rhyu, L. C. Abbott, D. B. Walker, C. Sotelo

Research output: Contribution to journalArticlepeer-review

84 Citations (Scopus)


Homozygous tottering (tg/tg) and compound heterozygous tottering/leaner (tg/tg(la)) mutant mice exhibit juvenile onset of three abnormal neurological phenotypes: (i) petit mal-like epilepsy; (ii) ataxia; and (iii) an intermittent myoclonus-like movement disorder. Homozygous leaner mice (tg(la)/tg(la)) exhibit early onset of ataxia (postnatal days 10-12), and also exhibit the myoclonus-like movement disorder and evidence of absence seizure activity; the myoclonus-like disorder is most evident in the first month of life, then diminishes in severity and frequency. The ultrastructure of the cerebellar molecular layer was examined in adult (six to eight months) and juvenile (20-25 days) mice of all three mutant genotypes. In mice of all three genotypes and both ages, Purkinje cell dendritic spines were observed to make multiple contacts with individual parallel fiber varicosities in all sections analysed. These multiple synaptic units were observed in both anterior and posterior vermis and hemispheres of the cerebellum, and ranged from two to nine spines/parallel fiber varicosity. Occasionally, one of the postsynaptic spines belonged to an ectopic spine emerging from the proximal region of a Purkinje cell dendrite. This increase in the multiple synaptic index of some parallel fiber varicosities was observed in juvenile tottering mice before the onset of the symptoms of the neurological disorders. This is highly suggestive that the onset of the neurological phenotype is not a primary cause of multiple Purkinje cell dendritic spines synapsing with single parallel fiber varicosities in these mice, but on the contrary, that it could be the cause of the ataxic symptoms.

Original languageEnglish
Pages (from-to)717-728
Number of pages12
Issue number3
Publication statusPublished - 1999 May
Externally publishedYes

Bibliographical note

Funding Information:
We would like to gratefully acknowledge Miles Frey for his help with sectioning of tissue for this ultrastructural study. This work was supported in part by a Fulbright Research Scholarship and an NIH grant (NS01681) to L.C.A., and the Kil Chung Hee Fellowship Fund to I.J.R.


  • Calcium channel mutation
  • Cerebellum
  • Genetic animal model
  • Myoclonus
  • Synaptogenesis

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'An ultrastructural study of granule cell/Purkinje cell synapses in tottering (tg/tg), leaner (tg(la)/tg(la)) and compound heterozygous tottering/leaner (tg/tg(la)) mice'. Together they form a unique fingerprint.

Cite this