NERVE GROWTH FACTOR-INDUCED SYNAPTOGENESIS AND HYPERTROPHY OF CORTICAL CHOLINERGIC TERMINALS

In this study light and EM quantitative analysis were used to examine whether exogenous nerve growth factor (NGF) could affect terminal fiel ds and synaptic connections in the adult rat brain in vivo. Adult rats received, immediately after unilateral decortication, 2.5S NGF (12-mu -g/day) or vehicle intracerebroventricularly for 7 days. Thirty days a fter the lesion cholinergic fiber length was quantified, using image a nalysis, in the remaining cortical area adjacent to the lesion site in each animal. Rats that had received vehicle showed a significantly re duced cortical choline acetyltransferase-immunoreactive fiber network in the remaining cortex when compared with control animals. By contras t, the network in lesioned rats that had received 2.5S NGF was not dif ferent from control animals. Furthermore, the number of cortical choli ne acetyltransferase-immunoreactive varicosities, which decreased in v ehicle-treated lesioned rats, significantly increased above control in lesioned rats that had received 2.5S NGF. At the ultrastructural leve l, 30 days after the lesion, animals that had received vehicle showed shrunken cholinergic boutons in cortical layer V and fewer synapses co mpared with control animals. Exogenous NGF, administered to lesioned r ats, increased to supernormal levels both size of cholinergic boutons and number of synaptic contacts. These parameters were unaltered in un lesioned rats treated with NGF. This study demonstrates that exogenous NGF can cause significant compensatory changes in terminal fields and synaptic connections in the adult fully differentiated central nervou s system.