Long-term effect of mossy fiber degeneration in the rat.

Mossy fiber-deafferentated rats (20) were permitted to survive from 34 to to 120 days and subsequently examined following Golgi-Cox preparation or after processing for electron microscopy. The primary response to mossy fiber deafferentation was transneuronal degeneration of the granule cell system. Morphological evidence is provided that suggests that the mossy fiber varicosity plays an important role in the fragmentation and removal of the granule cell digitiform dendrite. Computer-assisted image analysis of Golgi-impregnated Purkinje cells indicated significant losses in both smooth branch and spiny branchlet numbers following loss of the mossy fiber input. Ultrastructural examination revealed that a secondary transneuronal degeneration occurred within the dendritic arborization of both Purkinje cells and molecular layer interneurons. Although an overall reduction in the number of dendritic spines occurred along the terminal branchlets following mossy fiber deafferentation, several of the existing spines underwent marked changes in length, with some elongating to more than twice their size. By increasing the length of their spines, denervated Purkinje cells may acquire new synaptic contacts.