Inhibition of axoplasmic transport in the developing visual system of the rat-III. Electron microscopy and Golgi studies of retino-fugal synapses and post-synaptic neurons in the dorsal lateral geniculate nucleus.

Quantitative light and electron microscopy, together with Golgi methodology, were used to study alterations in retino-fugal terminals and postsynaptic neurons within the dorsal lateral geniculate nucleus of the rat at various intervals following inhibition of axoplasmic transport in the optic nerve induced by intraocular injections of colchicine from 1-20 days postnatal. Colchicine concentrations used in this study ranged from 10-5 M-10-2 M. These were selected on the basis of our measurements of axon transport suppression described in the preceding article. 61. The volume of the nucleus was determined by section planimetry and reconstruction. Growth of the contralateral dorsal lateral geniculate nucleus was significantly retarded by intraocular colchicine at 1 and 5 days of age, only achieving a volume of between 61-75% of the normal or the control (ipsilateral) nucleus depending upon dosage. Application of colchicine at 10 days of age resulted in minimal stunting of nuclear growth, (79-93% of normal). Mean numbers of neurons in the contralateral and ipsilateral nucleus remained stable throughout all postnatal ages examined suggesting that nuclear volume loss was caused principally by a reduction in the amount of neuropil. Golgi impregnation displayed dendritic stunting in relay neurons characterized by narrowing of the portion of the shaft between 40-80 micrometer from the soma and a reduced incidence of spinous protrusions, particularly those shown by other studies to engage the retino-fungal terminal. 27,69 A concomitant Sholl76 analysis of dendritic branching in relay neurons demonstrated no significant differences in the number of intersections between normal and experimental nuclei. No alterations were observed in intrinsic neurons. Electron microscopy of postsynaptic neurons following concentrations ranging from 10-4 M at birth revealed altered patterns of granular endoplasmic reticulum in many cells characterized by reduced numbers of cisternae and scattered instances of cisternal dilation, together with enhanced infolding of the nuclear membrane at 20 days postnatal. Those animals which were given 5 X 10-3 M-10-2 M colchicine demonstrated an increased incidence of cisternal dilation, loss of ribosomes, disruption of the nuclear membrane and occasionally, complete degeneration. A similar array of alterations took place following intraocular injection at 5 days of age; however, animals receiving colchicine at 10 days postnatal displayed minimal alterations in relay neurons. Synaptic glomeruli, which contain the retinofugal terminal, displayed dose and age-dependent reduction in the size of the presynaptic element of the complex following intraocular colchicine, together with fewer post-synaptic spinous protrusions. Synaptic vesicles remained normal in appearance and distribution and our quantitative analysis demonstrated no loss of such terminals in accordance with colchicine concentrations which were previously found not to be lethal to retinal ganglion cells and optic axons.