The process of reinnervation in the dentate gyrus of the adult rat: A quantitative electron microscopic analysis of terminal proliferation and reactive synaptogenesis

Abstract

The present study defined the time course of terminal proliferation (the growth of presynaptic processes) and reactive Synaptogenesis in the dentate gyrus of the adult rat. Quantitative electron microscopic analyses were carried out in the dentate gyrus 2, 4, 6, 8, 10, 12, 14 days and 7 months after destruction of the ipsilateral entorhinal cortex and in the contralateral (control) dentate gyrus. At each survival interval, counts were made from photographic montages of (1) terminals (presynaptic processes with or without contacts with postsynaptic elements), (2) intact synapses, (3) degenerating synapses, (4) degeneration (degenerating presynaptic processes), and (5) multiple synapses (terminals making more than one synaptic contact). Terminal density was initially reduced to about 13% of control in the middle molecular layer at 2 and 4 days postlesion, and to about 26% of control in the outer. The density of terminals began to increase between 4 and 6 days postlesion, reaching a plateau by day 12. Synapse density was reduced to about 8% and 12% of control in the middle and outer molecular layer respectively. Synapse density increased about 5‐fold between 8 and 12 days postlesion, but continued to increase in the period between 14 days and 7 months postlesion. At 2 days postlesion, the number of intact terminals that are lost corresponds to the number of degenerating presynaptic processes. This correspondence is not present at 4 days postlesion, however, suggesting a rapid removal of degenerating terminals. In contrast, even at 2 days post‐lesion, the number of intact synapses that are lost does not correspond to the number of degenerating synapses. Between 2 and 10 days postlesion, the number of postsynaptic specializations is about 60% of control, but recovers slightly by 12‐14 days postlesion. Qualitative and quantitative evidence suggested a collapse of spines into configurations that resembled shaft synapses. There appeared to be a deformation of degenerating presynaptic processes resulting in the appearance of multiple synapse configurations prior to reinnervation. The combined results suggest that terminal proliferation precedes reactive Synaptogenesis in the dentate gyrus by 2‐4 days, that terminal proliferation is essentially complete by 12 days while reactive Synaptogenesis continues, and that multiple synapses arise at least in part as a result of a deformation of degenerating presynaptic processes rather than as a consequence of the induction of additional contacts on existing presynaptic terminals.