Elsevier

Neuroscience

Volume 86, Issue 2, 1 June 1998, Pages 533-545
Neuroscience

Single-unit activity of cerebellar nuclear cells in the awake genetically dystonic rat

https://doi.org/10.1016/S0306-4522(98)00007-4Get rights and content

Abstract

The purpose of this study was to characterize neuronal activity in the deep cerebellar nuclei of the unanesthetized genetically dystonic rat during the neonatal period when the clinical signs of the dystonic syndrome first appear. Previous lesion studies have established cerebellar output as critical to the expression of the dystonic rat's motor syndrome, a disorder that closely resembles generalized dystonia in humans. In the dystonic rat, both cerebellectomy and selective lesions of the deep cerebellar nuclei decrease the frequency of abnormal motor signs and improve performance on tests of motor function. Single-unit activity was recorded from the medial, interpositus and lateral cerebellar nuclei in awake normal (N=49) and dystonic (N=54) rats at postnatal days 12–26. One hundred and eighty-three cells were isolated, 91 from normal and 92 from dt rats. Interspike interval histograms, autocorrelations and ratemeter histograms were generated for each cell's spike train. Interspike interval histograms were modeled with single and double gamma distributions. Cells from dystonic rats as young as 12 days of age showed bursting firing patterns, positively skewed or bimodal interspike interval histograms, and sinusoidal autocorrelations. Bursting activity increased linearly with postnatal age in dystonic rats. Cells from normal rats demonstrated non-sinusoidal autocorrelations and unimodal interspike interval histograms. Spike frequency increased linearly with postnatal age in both normal and dystonic rats.

There were no statistically significant group differences in spike frequency between normal and dystonic rats. These findings show that functional neuropathology can be detected at the level of single neurons in the deep cerebellar nuclei at the earliest behavioral stages of the dystonic rat's movement disorder. The degree of abnormality in spike train parameters correlates with the severity of the movement disorder. Independent of neuronal firing rates, abnormal neuronal firing patterns can serve as a guide to the localization of pathological cell populations within the central nervous system. These results provide additional evidence that abnormal cerebellar output plays a critical role in the pathophysiology of the dystonic rat's motor syndrome.

Section snippets

Animals and surgery

Single-unit activity was recorded from the MCN, INT and LCN in awake normal (N=49) and dt (N=54; Jfl:SD-dt) rats between and including P12 and P26. Dystonic pups were obtained from a breeding colony of Sprague–Dawley rats maintained at the University of Alabama at Birmingham. The 49 normal pups were the product of 26 dams. Twenty dams produced the 54 dt pups. All pups were housed with their dams until killing, and removed from their cages only for surgery and recording from the DCN. The animals

Results

Analysis of histological material revealed that recording sites were distributed throughout each cerebellar nucleus in both normal and dt rats. A representative spike train from a normal rat is presented in Fig. 1. The distinctive bursting patterns of DCN cells from dt rats at several postnatal ages is seen in Fig. 2Fig. 3Fig. 4Fig. 5. The spike trains from normal rats exhibited occasional bursts of variable duration; bursts of two spikes (doublets) are seen in Fig. 1. In contrast, the number

Discussion

Single-unit recordings from the MCN, INT and LCN in the awake dt rat support the conclusions of lesion studies by showing that the cerebellar output signal from each of the DCN is abnormal.10, 11, 12 In the awake preparation, DCN neuronal firing rates were not statistically different (α=0.05) between normal and dt rats. However, the pattern of firing was markedly different. DCN cells from dt rats showed frequent, short bursts of only two to five spikes. In addition, the short bursts of spikes

Conclusions

Single-unit recordings were obtained from the DCN in awake normal and dt rats from P12 to P26. Cells from dt rats demonstrated prominent rhythmic bursting activity that increased linearly with postnatal age. Functional neuropathology was detected in the DCN at the earliest stages of the dt rat movement disorder. There were no statistically significant differences in DCN spike frequency between normal and dt rats. These results are consistent with previous lesion studies which demonstrated a

Acknowledgements

This work was supported by grants from the National Institute of Neurological Disorders and Stroke (K08 NS01593-01) and the Dystonia Medical Research Foundation.

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