Inhibition of axoplasmic transport in the developing visual system of the rat: IV. Quantitative Golgi, electron microscopic, and histochemical analyses of the maturation of the visual cortex.

Intraocularly injected colchicine suppresses axonal transport within the developing rat's optic nerve throughout the critical period of visual system development. This results in a stunting of retinofugal terminals and relay neurons in the lateral geniculate nucleus. The present study focuses upon the effects of this unique form of developmental deprivation on the maturation of the visual cortex. Colchicine, in concentrations of from 10(-5) to 10(-2) M, was injected into the eyes of albino rats at birth or at 5, 10, or 15 days of age. Litters were killed at 5 to 50 days after this single injection, and the brains were processed for Nissl, rapid Golgi, histochemical, or electron microscopic analysis. The following results were obtained: Planimetry of coronal sections of the striate cortex revealed a reduction in the thickness of the cortex and in the ratio of neuropil area to neuronal soma area contralateral to the injected eye which was confined principally to layer IV, lower layer III, and upper layer V. This effect was inversely related to postnatal age at injection and directly proportional to colchicine concentration. A rapid Golgi analysis of 51 pairs of layer V pyramidal neurons in control and experimental cortex demonstrated a reduction in the number and size of spines along the portion of the apical dendrite passing through lower layer III and IV following colchicine administration at birth or 5 or 10 days of age but no significant change in the branching pattern of the entire dendritic arbor. Electron microscopy revealed a reduction in the number of small, asymmetric synaptic complexes with the result that the average size of remaining profiles was increased in layers III and IV. Histochemical analysis of cortical succinic dehydrogenase and cytochrome oxidase revealed a distinct band of intense enzyme activity in lower layers III and IV in normal cortex at 20-30 days of age. This band was significantly reduced in intensity after neonatal injection of colchicine as shown by densitometric measurements and comparison of experimental and control cortex. It is concluded that the geniculocortical projection, while not affected directly by colchicine administration, is altered by the secondary effects of axonal transport suppression, leading to an alteration in the establishment of cortical synaptic patterns and arborizations of their postsynaptic neurons whose dendrites are located in those layers recipient to this projection.