Cytosine arabinoside effects on developing cerebellum in tissue culture

Abstract

Cerebellar explants derived from neonatal mice were exposed to cytosine arabinoside, an inhibitor of DNA synthesis. Following such exposure, the cortical regions of the explants contained numerous closely packed large neurons with few intervening elements and without lamination. The surviving large cortical neurons included Golgi cells and Purkinje cells, the latter with persistent dendritic spines in the absence of granule cells. A marked increase in density of subcortical and intracortical neurites was evident in fiber stains. The neurites were identified as Purkinje cell axons and axon collaterals by fiber tracing. Myelin failed to form around the axonal elements. Both regular and phasic spontaneous discharges were recorded electrophysiologically. Trains of cortical stimuli elicited both excitatory and inhibitory responses in the absence of parallel fibers. Antidromic stimulation of Purkinje cell axon evoked inhibition of spontaneous cortical discharges. By contrast, antidromic activation of Purkinje cell axons in control cultures had no effect on spontaneous cortical discharges, or provoked a transient increase in discharge rate. These responses were interpreted as consistent with a cortical remodeling in granuloprival cerebellar cultures in which basket-stellate cell inhibition of Purkinje cells was preemted by Purkinje cell recurrent axon collateral inhibition.