The effects of nerve growth factor and its antiserum on synapses in the superior cervical ganglion of the guinea-pig.

1. The effects of nerve growth factor (NGF) and its antiserum on synapses in the superior cervical ganglion of the guinea-pig have been examined by intracellular recording and electron microscopy. 2. Exogenous NGF, supplied locally from a silicone rubber pellet implanted near ganglia for 4-7 days, had little effect on either the function or the number of ganglionic synapses. 3. However, the depression of synaptic transmission and loss of synaptic contacts on ganglion cells which follow post-ganglionic axotomy were diminished by about 50% in the presence of exogenous NGF. 4. Other post-axotomy changes such as the development of subthreshold regenerative responses in neuronal processes, the appearance of ultrastructurally abnormal neuronal profiles suggesting rapid membrane turnover, and the cytoplasmic and nuclear changes characteristic of "chromatolysis", were also largely prevented by exogenous NGF. 5. Systemic treatment of neonatal and young adult guinea-pigs with antiserum to NGF for 4-5 days caused depression of intracellularly recorded synaptic responses within 5-8 days of the end of antiserum administration. Synapse counts in electron microscopical sections from these ganglia showed only about half as many contacts as in control ganglia from animals receiving normal rabbit serum. 6. These findings suggest that the loss of synapses from sympathetic neurones which follows axotomy results from a reduction in the amount of NGF supplied to ganglion cells. A corollary is that, among other biological roles, NGF is required by peripheral sympathetic neurones to maintain the synapses they receive.