Accelerated rates of synaptogenesis by "sprouting" afferents in the immature hippocampal formation.

Abstract

Light and electron microscopic methods were used to study the rate with which undamaged afferents sprout into and form synapses within denervated dendritic zones in the immature rat brain. The middle and outer molecular layers of the dentate gyrus were deafferented by ablation of the ipsilateral entorhinal cortex in 14-day-old rats, and the extension of the commissural projections, which are normally restricted to the inner molecular layer, into the denervated territory was studied by light microscopic autoradiographic tracing methods. Collateral growth was noted as early as 13 hours after the lesion and was found to reach throughout the middle and outer molecular layers by 48 hours postlesion. Quantitative analyses (grain counts) revealed that the addition of commissural fibers and terminals to the denervated zones proceeded extremely rapidly up to 72 hours after the removal of the entorhinal cortex, but slowed markedly thereafter. Electron microscopic procedures were used to assess the rate at which synapses formed during this period and yielded the following information: 1) The density of intact synapses fell to below 20% of normal values within 20 hours of the lesion, 2) reinnervation began before 30 hours postlesion, and 3) the rate at which synapses were added to deafferented middle molecular layer was much more rapid from 20-96 hours postlesion than is observed in this zone during normal development. Furthermore, the sprouting of the inner molecular layer afferents into the middle molecular layer did not retard the pace of synaptogenesis in their normal target region. These results suggest that intrinsic limitations in the capacity of axons and dendrites are not responsible for determining the rate of synaptogenesis in the developing hippocampus. It is proposed instead that existing synapses (or terminals and spines) tend to suppress the formation of new contacts such that the local density of connections regulates the speed with which further innervation occurs.