Purkinje cell input to cerebellar nuclei in tottering: ultrastructure and physiology

Cerebellum. 2008;7(4):547-58. doi: 10.1007/s12311-008-0086-0. Epub 2008 Dec 11.

Abstract

Homozygous tottering mice are spontaneous ataxic mutants, which carry a mutation in the gene encoding the ion pore of the P/Q-type voltage-gated calcium channels. P/Q-type calcium channels are prominently expressed in Purkinje cell terminals, but it is unknown to what extent these inhibitory terminals in tottering mice are affected at the morphological and electrophysiological level. Here, we investigated the distribution and ultrastructure of their Purkinje cell terminals in the cerebellar nuclei as well as the activities of their target neurons. The densities of Purkinje cell terminals and their synapses were not significantly affected in the mutants. However, the Purkinje cell terminals were enlarged and had an increased number of vacuoles, whorled bodies, and mitochondria. These differences started to occur between 3 and 5 weeks of age and persisted throughout adulthood. Stimulation of Purkinje cells in adult tottering mice resulted in inhibition at normal latencies, but the activities of their postsynaptic neurons in the cerebellar nuclei were abnormal in that the frequency and irregularity of their spiking patterns were enhanced. Thus, although the number of their terminals and their synaptic contacts appear quantitatively intact, Purkinje cells in tottering mice show several signs of axonal damage that may contribute to altered postsynaptic activities in the cerebellar nuclei.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Animals
  • Ataxia / genetics*
  • Ataxia / physiopathology*
  • Calbindins
  • Calcium Channels, Q-Type / genetics
  • Calcium Channels, Q-Type / physiology*
  • Cerebellar Nuclei / growth & development
  • Cerebellar Nuclei / physiology*
  • Cerebellar Nuclei / physiopathology
  • Cerebellar Nuclei / ultrastructure
  • Crosses, Genetic
  • Electroencephalography
  • Electrophysiology
  • Female
  • Male
  • Mental Disorders / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Neurologic Mutants / physiology*
  • Nerve Endings / physiology
  • Nerve Endings / ultrastructure
  • Polymerase Chain Reaction
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • S100 Calcium Binding Protein G / analysis

Substances

  • Calbindins
  • Calcium Channels, Q-Type
  • S100 Calcium Binding Protein G