Synaptic integration in sympathetic ganglia and in midbrain dopamine neurons.

We study synaptic regulation of information processing in neural circuits. In sympathetic ganglia, the wiring of connections is simple, but the circuit contains a rich diversity of synaptic mechanisms. Presynaptic release of acetylcholine transmits fast synaptic excitation via nicotinic receptors and slow synaptic modulation in several forms via muscarinic receptors. We exploit this well-defined organization to investigate fundamental rules that govern the slow metabotropic modulation of fast ionotropic synapses.

By combining experimental and computational methods we developed a mathematical theory of ganglionic integration. It predicts that sympathetic ganglia function as variable synaptic amplifiers. In this framework, nicotinic synapses and presynaptic activity are the basic determinants of synaptic gain, while muscarinic mechanisms and other forms of short-term synaptic plasticity serve to regulate synaptic gain.

These ideas are significant because of their implications for the regulation of important autonomic behaviors, which include cardiovascular adaptation to exercise, thermoregulation, sexual mating, adaptation to stress, and cognitive arousal. To date, the most direct experimental evidence for ganglionic gain has come from studies of secretomotor sympathetic B neurons in the bullfrog. Our present work aims to generalize the synaptic gain hypothesis by extending experimental studies to vasomotor sympathetic C neurons in the bullforg and to homologous cell types in rat sympathetic ganglia.

The amphibian studies employ whole-cell perforated-patch recording together with the dynamic clamp method in order to create computer-generated virtual synapses on living neurons. The results indicate that vasomotor and secretomotor neurons do in fact have different integrative properties.

Meanwhile, separate microelectrode studies of the rat superior cervical ganglion have permitted us to develop anatomical and electrophysiological criteria that allow for the functional identification of different mammalian sympathetic cell types and an analysis of their integrative properties.

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Important Publications

Kullmann PH and JP Horn. Excitatory muscarinic modulation strengthens virtual nicotinic synapses on sympathetic neurons and thereby enhances synaptic gain. J Neurophysiol 96(6):3104-3113, 2006.

Hahn J, PH Kullmann, JP Horn and ES Levitan. D2 Autoreceptors chronically enhance dopamine neuron activity. Journal of Neuroscience 26:5240-5247, 2006.

Li CC and JP Horn. Physiological classification of sympathetic neurons in the rat superior cervical ganglion. J Neurophysiol 95:187-195, 2005.

Headley DB, NH Suhan and JP Horn. Rostro-caudal variations in neuronal size reflect the topography of cellular phenotypes in the rat superior cervical sympathetic ganglion. Brain Research 1057:98-104, 2005.

Wheeler DW, PH Kullmann and JP Horn. Estimating use-dependent synaptic gain in autonomic ganglia by computational simulation and dynamic-clamp analysis. J Neurophysiol 92:2659-2671, 2004.