Role_1988_Proc.Natl.Acad.Sci.U.S.A_85_2825

The development of transmitter sensitivity is an important component of synaptic differentiation. Despite a wealth of information about the appearance of acetylcholine (AcCho) sensitivity at the neuromuscular junction, the onset and regulation of this critical aspect of synaptogenesis has not previously been examined for synapse formation between neurons. To determine whether there is a role of presynaptic input in the induction of AcCho sensitivity at interneuronal synapses, AcCho-induced currents were measured in embryonic sympathetic neurons before and after synapse formation in vitro. The total AcCho sensitivity of postsynaptic neurons was increased nearly 10-fold after innervation. The effects of innervation are mimicked by medium conditioned by preganglionic neurons, suggesting that presynaptic neurons regulate postsynaptic AcCho sensitivity by release of a soluble factor. These observations provide evidence that presynaptic input regulates neuronal sensitivity to an identified synaptic transmitter.