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Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the awake genetically dystonic rat

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Abstract

The genetically dystonic rat is an autosomal recessive mutant with a movement disorder that closely resembles the generalized dystonias seen in humans. Abnormal activity of neurons within the cerebellar nuclei is critical to the dystonic rat motor syndrome. Increased glutamic acid decarboxylase activity, increased glucose utilization, and decreased muscimol binding within the cerebellar nuclei of the dystonic rat suggests that Purkinje cell firing rates are increased in these animals. However, under urethane anesthesia, Purkinje cell simple spike firing rates in dystonic rats were less than half the rates seen in normal littermates. In this study, both spontaneous and harmaline-stimulated single-unit Purkinje cell recordings were obtained from awake normal and dystonic rats. In striking contrast to previous results obtained under urethane anesthesia, there was no statistically significant difference in average Purkinje cell spontaneous simple spike frequency between dystonic and normal rats. Similar to previous studies obtained under urethane anesthesia, Purkinje cell spontaneous complex spike frequency was much lower in dystonic than in normal rats. Many Purkinje cells from dystonic rats, particularly those from the vermis or older animals, exhibited rhythmic bursting simple spike firing patterns. Crosscorrelations showed that complex spikes produced less suppression of simple spikes in dystonic than in normal rats and harmaline-stimulated complex spike activity was, on average, faster and more rhythmic in normal than in dystonic rats. These findings indicate that olivocerebellar network abnormalities in the dystonic rat are not due to an inability of Purkinje cells to fire at normal rates and suggest that abnormal Purkinje cell bursting firing patterns in the dystonic rat are due to a defect in the pathway from the inferior olive to climbing fiber synapses on Purkinje cells.

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Author information

Correspondence to Mark S. LeDoux.

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LeDoux, M.S., Lorden, J.F. Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the awake genetically dystonic rat. Exp Brain Res 145, 457–467 (2002). https://doi.org/10.1007/s00221-002-1127-4

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Keywords

  • Dystonia
  • Inferior olive
  • Bursting
  • Autocorrelation
  • 3-Acetylpyridine