This talk introduces a symposium focusing on current efforts to dissect nicotinic and non-nicotinic mechanisms of synaptic transmission in autonomic ganglia and their integrative consequences in health and disease. We begin with a general theory of ganglionic integration. This framework incorporates basic features of synaptic divergence and convergence that operate in most paravertebral sympathetic ganglia. The goal is to reconstruct the integrative properties of ganglia from the bottom up beginning with nicotinic synapses and using information from the literature describing natural patterns of activity observed in experimental animals and in awake human subjects. The results imply that sympathetic ganglia behave as variable synaptic amplifiers whose gain is regulated by activity, nicotinic synaptic strength and the expression of neuromodulatory G-protein coupled receptors. More specifically, gain theory predicts that up to 98% of postganglionic activity originates in sympathetic ganglia, outside the central nervous system and that ganglionic gain can easily double the frequency of sympathetic activity. We will present recent unpublished experiments designed to replicate rhythmic activity observed in barosensitive muscle vasoconstrictor neurons and renal sympathetic neurons. Using dynamic clamp to create complex patterns of virtual synaptic activity, we find that entraining preganglionic activity to the cardiac cycle can increase synaptic gain and that modulation by angiotensin II can also increase gain. Simulating an increase in sympathetic drive, as occurs in exercise and in essential hypertension, also has the effect of increasing gain. By comparing these results with data from other groups, we will argue that similar mechanisms of ganglionic gain may operate in the human sympathetic ganglia. All of the new experiments described in this talk are based on whole cell recordings from dissociated mammalian sympathetic neurons in the rat superior cervical ganglion. This work was supported by NIH and by the University of Pittsburgh School of Medicine.
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Received: May 15, 2013
© 2013 Published by Elsevier Inc.