The integrative role of synaptic cotransmission in the bullfrog vasomotor C system: evidence for a synaptic gain hypothesis.

Understanding the integrative significance of synaptic cotransmission is a central problem in autonomic physiology. What are the functional roles of slow synaptic potentials in autonomic ganglia? This paper reviews the problem and its historical roots by focusing on work in the amphibian paravertebral sympathetic system. The phenotypic properties that distinguish the sympathetic B and C cell systems are summarized. Then, a synaptic gain hypothesis is proposed for the integrative function of muscarinic and peptidergic synapses in the vasomotor C system. The model states that the peripheral output of the vasomotor system is subject to synaptic amplification by two gain stages in series. The first gain stage is postulated to arise in ganglia from interactions between two slow postsynaptic potentials; the excitatory response mediated by luteinizing hormone releasing hormone, and the inhibitory response mediated by the muscarinic action of acetylcholine. The second gain stage is postulated to arise in arteries from interactions between two postganglionic cotransmitters: epinephrine and neuropeptide Y. A circuit with these properties would enable preganglionic patterns of electrical activity to regulate the system's output over a wider dynamic range than possible without cotransmitters.