Dynamic clamp analysis of synaptic integration in sympathetic ganglia

Advances in modern neuroscience require the identification of principles that connect different levels of experimental analysis, from molecular mechanisms to explanations of cellular functions, then to circuits, and, ultimately, to systems and behavior. Here, we examine how synaptic organization of the sympathetic ganglia may enable them to function as use-dependent amplifiers of preganglionic activity and how the gain of this amplification may be modulated by metabotropic signaling mechanisms. The approach combines a general computational model of ganglionic integration together with experimental tests of the model using the dynamic clamp method. In these experiments, we recorded intracellularly from dissociated bullfrog sympathetic neurons and then mimicked physiological synapses with virtual computer-generated synapses. It, thus, became possible to analyze the synaptic gain by recording cellular responses to complex patterns of synaptic activity that normally arise in vivo from convergent nicotinic and muscarinic synapses. The results of these studies are significant because they illustrate how gain generated through ganglionic integration may contribute to the feedback control of important autonomic behaviors, in particular to the control of the blood pressure. We dedicate this paper to the memory of Professor Vladimir Skok, whose rich legacy in synaptic physiology helped to establish the modern paradigm for connecting multiple levels of analysis in studies of the nervous system.