A new type of lesion-induced synaptogenesis: II. The effect of aging on synaptic turnover in non-denervated zones.

Partial denervation of the dentate molecular layer causes sprouting and reinnervation by undamaged afferents within the denervated zones of young adult animals and to a lesser extent in aged animals. We have previously reported a non-degenerative remodeling of the dentate molecular layer in areas outside the primary denervated zone of young adult rats after a unilateral entorhinal lesion. In this study, we evaluate the response of aged rats under the same conditions, to see if aged animals also respond to injury in non-denervated zones. After a unilateral entorhinal lesion, the outer two-thirds of the ipsilateral dentate molecular layer loses about 85% of its input, while the outer two-thirds of the contralateral molecular layer loses less than 5% of its input (crossed temporo-dentate path). Denervation does not occur in the inner one-third of the molecular layer on either side. Within the ipsilateral inner molecular layer, the synaptic density rapidly drops 21% in the absence of degeneration and then recovers by 10 days post-lesion, as is the case in young adult animals. On the contralateral side, young adult animals show synapse turnover similar to the ipsilateral inner molecular layer. In contrast, no significant response in the total synaptic density was observed in the non-denervated contralateral inner molecular layer or the partially denervated outer two-thirds of the contralateral molecular layer. Thus, in aged animals, synaptic turnover is restricted to the massively denervated ipsilateral side. The small loss of input to the contralateral side apparently is not sufficient to initiate quantifiable turnover of synaptic contacts. This steady-state situation may be the result of an on-going stabilization of neuronal circuitry, which may limit restoration of function after injury in aged animals.