Chronic NMDA receptor blockade or muscimol inhibition of cerebellar cortical neuronal activity alters the development of spinocerebellar afferent topography

D. L. Tolbert, T. Pittman, J. M. Alisky, B. R. Clark

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

The requirement for cerebellar cortical neuronal activity in the development of spinocerebellar afferent topography was investigated in neonatal rats. In adult rats lower thoracic-upper lumbar spinocerebellar projections are localized to sharply circumscribed patches in the granule cell layer of the cerebellar anterior lobe. In transverse sections these patches appear as sagittally oriented stripes. This pattern develops postnatally as many spinal axons which initially project between the incipient stripes are eliminated thereby sharpening the stripe boundaries. We attempted to alter cerebellar cortical neuronal activity in neonatal animals to study the effects of these changes on the development of spinocerebellar stripes. In some experiments glutaminergic excitatory synaptic transmission was chronically blocked with the N-methyl-d-aspartate (NMDA) receptor antagonist 2-aminophosphovaleric acid (APV). In other experiments postsynaptic activity was directly inhibited by the γ-aminobutyric acid agonist muscimol. Chronic exposure to APV or to muscimol did not affect the initial development of spinocerebellar projections; many spinal axons were present in the anterior lobe and arranged in incipient stripes. Both the APV and the muscimol appeared to prevent the elimination of interstripe projections; consequently the boundaries of the stripes remained poorly defined. These findings suggest that cerebellar cortical neuronal activity is a necessary requirement for the refinement of spinal afferent topography in the anterior lobe.

Original languageEnglish
Pages (from-to)268-274
Number of pages7
JournalDevelopmental Brain Research
Volume80
Issue number1-2
DOIs
StatePublished - Jul 15 1994

Bibliographical note

Funding Information:
Supported by NIH Grant NS-20227. The authors thank the DuPont corporation for their generous gift of Elvax and C. Pollack for his assistance with photography.

Funding

Supported by NIH Grant NS-20227. The authors thank the DuPont corporation for their generous gift of Elvax and C. Pollack for his assistance with photography.

FundersFunder number
National Institutes of Health (NIH)
National Institute of Neurological Disorders and StrokeR01NS020227

    Keywords

    • 2-Aminophosphovalerate
    • Cerebellum
    • Map formation
    • Muscimol
    • N-Methyl-d-aspartate
    • Spinocerebellar

    ASJC Scopus subject areas

    • Developmental Neuroscience
    • Developmental Biology

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