The role of cyclic AMP in the modulation of synaptic efficacy.

1. Heterosynaptic facilitation (modification of synaptic transmission by a neuron influencing the terminals of the presynaptic neuron) was studied in the pleural ganglion of Aplysia. Among several identified synapses, heterosynaptic facilitation was observed only in one type (EIPSP synapses) when repetitive stimulation was applied to the tentacular nerve or to a particular identified neuron. 2. Serotonin was shown to increase the amplitude of the EIPSP at this synapse; this facilitatory effect was prolonged in the presence of theophylline and mimicked by cyclic AMP. 3. When transmission was abolished by calcium-free solution, calcium injected in the region of the synapse caused partial recovery of the EIPSP; when calcium injection was preceded by serotonin injection near the same terminal, the EIPSP was much larger than with calcium injection alone. 4. It was concluded that the activation of one neuron (the heterosynaptic neuron) caused it to release serotonin, which activated an adenylate cyclase in the pre-synaptic terminals of another neuron. Consequent accumulation of cyclic AMP in these terminals is supposed to have increased their voltage-dependent calcium conductance and hence the amount of transmitter released during an action potential.