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A measure of striatal function predicts motor stereotypy

Nature Neuroscience volume 3, pages 377–383 (2000)Cite this article

Abstract

To identify basal ganglia circuit dysfunctions that might produce repetitive behaviors known as motor stereotypies, we applied psychomotor stimulants and a direct dopamine receptor agonist to induce different levels of stereotypy in rats. We then used a gene induction assay to measure the functional activation of neurons in the neurochemically distinct compartments of the striatum, the striosomes and the extrastriosomal matrix. The amount by which activation in the striosomes exceeded activation in the matrix predicted the degree of motor stereotypy induced by the drug treatments. These results suggest that imbalance between compartmentally organized basal ganglia circuits may represent a neural correlate of motor stereotypy.

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Figure 1: Cocaine, amphetamine and apomorphine treatments induce motor stereotypy and increased relative striosomal activation (ISMP ratios) in the caudoputamen.
Figure 2: Fos expression in the striosomal compartment is increased relative to expression in the matrix by chronic psychomotor stimulant treatments and by increasing doses of apomorphine.
Figure 3: Striosome-predominant pattern of Fos staining occurs with chronic amphetamine treatment.
Figure 4: Correlations between drug-induced motor stereotypy and gene-based measures of striatal activation are highest for lateral ISMP values for the three drug treatments examined.
Figure 5: Close parallels between stereotypy scores and ISMP values occur despite different combinations of up- and downregulation of gene expression in the individual striosome and matrix compartments.
Figure 6: Correlations between averaged ISMP values and stereotypy values are high for each of the experimental treatments studied.

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Acknowledgements

This work was funded by NIDA R01 DA08037, the National Parkinson Foundation, the Stanley Foundation and the Grayce B. Kerr Fund. We thank Patricia Harlan for technical assistance, Henry Hall for the photography, Joel Ventura and Paul Di Zio for advice on statistics and R. Bravo, R. P. Elde, M. Iadarola and S. Watson for their gifts of antisera.

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  1. Juan J. Canales

    Present address: Department of Neurobiology, Instituto de Investigaciones Citológicas, Fundación Valenciana de Investigaciones Biomédicas, Amadeo de Saboya 4, 46010, Valencia, Spain

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  1. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton St., E25-618, Cambridge, 02139, Massachusetts, USA

    Juan J. Canales & Ann M. Graybiel

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Correspondence to Ann M. Graybiel.

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Canales, J., Graybiel, A. A measure of striatal function predicts motor stereotypy. Nat Neurosci 3, 377–383 (2000). https://doi.org/10.1038/73949

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