Degeneration of thalamic neurons in “Purkinje cell degeneration” mutant mice. II. Cytology of neuron loss

Abstract

The cytology of thalamocortical relay neuron degeneration in the ventral medial geniculate nucleus (vMG) of mice homozygous for the autosomal recessive Purkinje cell degeneration (pcd) mutation has been studied by light and electron microscopy. More limited sampling of the submedial and mediodorsal nuclei suggested that cytological alterations in the vMG were typical of all degenerating thalamic nuclei. The number of vMG neurons in pcd mutants was comparable to controls at and prior to postnatal day 40 (P40). By P60 seventy percent, and by P90 approximately 9%, of the original complement of vMG neurons had degenerated in mutant mice. At P30, the general cytological organization of vMG neurons closely resembled that of neurons in littermate (+/+ or +/pcd) controls, but neurons in mutants were distinguished by the presence of small aggregates of fine granules (approximately 9 nm in diameter) that were commonly associated with otherwise normal cisternae of rough endoplasmic reticulum; neither the number nor the size of these granular aggregates increased in older mutants. By P50 cytoplasmic organelles were curiously distributed in more severely affected neurons: large areas of cytoplasm were occupied exclusively by polysomes, while profiles of endoplasmic reticulum and the Golgi apparatus appeared to be reduced. Before frank degenerative changes were apparent (at P50), all classes of synaptic terminals identified in normal mice were found to have made morphologically normal synaptic contacts on mutant vMG neuron dendrites. In contrast to the homologous nuclear complex in the cat, presynaptic dendrites were not apparent in synaptic glomeruli in wild‐type or mutant murine vMG. Cytopathological alterations in the neuropil of P50 and older mutants were dominated by degenerating dendritic profiles; there was no evidence that the loss of thalamic neurons in pcd mutants was associated with synaptic agenesis or dysgenesis or the prior or concurrent degeneration of afferent synaptic terminals.