Degeneration of thalamic neurons in "Purkinje cell degeneration" mutant mice. I. Distribution of neuron loss.

The Purkinje cell degeneration (pcd) mutation of the mouse is an autosomal recessive allele which previous studies have shown to be the cause of rapid degeneration of nearly all cerebellar Purkinje cells between 18 and 30 postnatal days of age (P18-P30), and slowly developing, progressive losses of retinal photoreceptor cells and mitral cells of the olfactory bulb. Through examination of serial frozen sections alternately stained for Nissl substance and for degenerating neuronal processes, we have found that discrete populations of thalamic neurons degenerate rapidly between P50 and P60. Severely affected nuclei, in which a majority of neurons degenerate, include the central division of the mediodorsal nucleus, the ventral medial geniculate, posterior, posterior ventromedial, and submedial nuclei, and those portions of the ventrolateral and posteromedial nuclei which immediately surround the medial division of the ventrobasal complex. More subtle cell losses occur during the same time period in restricted portions of the lateral ventrobasal, dorsal lateral geniculate, and lateral posterior nuclei, but even at P180 these nuclei are not markedly atrophic. No common denominator among target cell populations has been established. The pcd allele affects a diverse assortment of specific relay nuclei; degeneration has not been recognized in thalamic nuclei characterized primarily or exclusively by subcortical projections or by cortical projections directed relatively selectively to superficial or deep cortical laminae. The neuronal degenerations in the thalamus are not precipitated by prior or concurrent degeneration of cortical targets or afferent sources, though striking transneuronal changes, including cell death, do develop following thalamic neuronal degeneration in this mutant. No previously described murine mutant phenotype includes the rapid degeneration of highly restricted neuronal populations beginning at these relatively advanced ages.