Neuronal maturation and synaptogenesis in the rat ventrobasal complex: alignment with developmental changes in rate and severity of axon reaction.

Developmental alterations in the rate and severity of axon reaction are thought to be influenced by the level of neuronal maturation and synaptogenesis. As an initial step in more carefully examining this issue, two concurrent series of studies were performed using the ventrobasal complex as a model. Sprague-Dawley albino rats, ranging in age from neonate through 60 days postnatal (dpn) were subjected to unilateral aspiration lesions encompassing somato-sensory cortex. Two to four animals were sacrificed at various postoperative periods of from one through 40 days. The reactive ventrobasal (VB) complex was qualitatively and quantitatively analysed employing electron microscopy and the Cajal-DeCastro reduced silver technique or a hematoxylin-eosin-Orange-G method for light microscopic study. Neuronal degenerative changes are prominent within 48 hours following ablation of neonate through 9 dpn animals. These alterations include a loss of cytoplasmic basophilia together with vacuolization, and rapid disappearance of the cell. Swelling and vacuolization of axons and dendrites is seen throughout the zone of degeneration accompanied by the rapid accumulation of numerous reactive non-neuronal elements, some of which resemble those mesodermal elements designated as “M” cells. Following equivalent lesions of animals 12 through 60 dpn, neurons within the VB undergo degenerative changes which are qualitatively similar to those seen in younger animals but require between 6 and 20 days postoperative to appear. While most such cells will disappear the degenerative process is temporally extended by as much as one order of magnitude. The normal ventrobasal complex was examined in 7,12,15,20, and 60 dpn rats. Golgi-Cox impregnations of thalamic neurons reveal such cells at 7 dpn to be characterized by short, stubby, irregular dendrites with distinct growth cones and filopodia, whereas by 12 dpn Golgi analysis demonstrates prominent morphological changes indicative of considerable progress in thalamic neuronal differentiation including dendritic elongation with secondary and tertiary branching, and the appearance of spinous protrusions. The use of the Rasmussen stain for synapses, as well as electron microscopy, shows distinctive trends of synaptogenesis typified by a paucity of synaptic complexes but large numbers of dendritic and axonal growth cones at 7 dpn. However, by 12 dpn a 3-fold increase in the number of synapses has taken place together with an enhanced morphological complexity and variety of individual synaptic profiles, some of which are known to represent lemniscal input. Further prominent increases in synaptic population density are observed at 15dpn but the rate of synaptogenesis appears to become attenuated after this period. Finally, patterns of distribution of perikaryal RNA become altered from a predominance of polyribosomes at 7 dpn to characteristic multilamellate aggregations of granular endoplasmic reticulum initially observed at 12 dpn. With subsequent neuronal enlargement this component proportionally increases in amount but is qualitatively unchanged with respect to morphological arrangement. The close temporal correlation between the specific developmental events documented in this study and the postnatal age during which VB neurons become less susceptible to injury suggests that important changes in maturation of intrinsic neuronal metabolism involving rates of RNA and protein synthesis may be, in part, initiated and regulated by extrinsic factors related to the establishment of pre-synaptic input upon VB neurons. A number of putative molecular substrates for these influences are discussed.