CHRONIC NMDA RECEPTOR BLOCKADE OR MUSCIMOL INHIBITION OF CEREBELLAR CORTICAL NEURONAL-ACTIVITY ALTERS THE DEVELOPMENT OF SPINOCEREBELLAR AFFERENT TOPOGRAPHY

The requirement for cerebellar cortical neuronal activity in the devel opment of spinocerebellar afferent topography was investigated in neon atal rats. In adult rats lower thoracic-upper lumbar spinocerebellar p rojections are localized to sharply circumscribed patches in the granu le cell layer of the cerebellar anterior lobe. In transverse sections these patches appear as sagittally oriented stripes. This pattern deve lops postnatally as many spinal axons which initially project between the incipient stripes are eliminated thereby sharpening the stripe bou ndaries. We attempted to alter cerebellar cortical neuronal activity i n neonatal animals to study the effects of these changes on the develo pment of spinocerebellar stripes. In some experiments glutaminergic ex citatory synaptic transmission was chronically blocked with the N-meth yl-D-aspartate (NMDA) receptor antagonist 2-aminophosphovaleric acid ( APV). In other experiments postsynaptic activity was directly inhibite d by the gamma-aminobutyric acid agonist muscimol. Chronic exposure to APV or to muscimol did not affect the initial development of spinocer ebellar projections; many spinal axons were present in the anterior lo be and arranged in incipient stripes. Both the APV and the muscimol ap peared to prevent the elimination of interstripe projections; conseque ntly the boundaries of the stripes remained poorly defined. These find ings suggest that cerebellar cortical neuronal activity is a necessary requirement for the refinement of spinal afferent topography in the a nterior lobe.