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 bullfrog 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.

A second goal of our research is to extend concepts and methods from autonomic ganglia to circuits in the central nervous system.  For this, we are studying midbrain dopamine neurons in a collaborative project that began in Professor Edwin Levitan’s laboratory in the Department of Pharmacology.  Working together the Levitan and Horn labs have found that chronic exposure to antipsychotic drugs can alter A-type potassium channel expression by midbrain dopaminergic neurons located in the ventral tegmental area and substantia nigra.  These cells are of wide interest because they play pivotal roles in modulation of motor behavior, motivation and emotion.  Their disruption has been implicated in Parkinson’s disease, drug addiction including tobacco use, attention deficit disorder and schizophrenia.  Our approach combines molecular biology, brain slice electrophysiology and the dynamic-clamp method to investigate synaptic mechanisms that control the intrinsic electrical pacemaking activity of dopaminergic neurons and its disruption by drugs used to treat affective disorders.

Graduate students, undergraduates and postdoctoral fellows in the Horn lab pursue a multidisciplinary approach to neural circuit analysis, focused at the cellular, molecular and theoretical levels.

Sample Publications:
see also publications on the Horn Lab website

Kullmann, P.H., Wheeler, D.W., Beacom, J., and Horn, J.P.  Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT. J. Neurophysiol. 91: 542-54, 2004.

Wheeler, D.W., Kullmann, P.H., and Horn, J.P. Estimating use-dependent synaptic gain in autonomic ganglia by computational simulation and dynamic-clamp analysis. J. Neurophysiol. 92: 2659-71, 2004.

Headley, D.B., Suhan, N.M. and Horn, J.P.  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.

Li, C. and Horn, J.P. Physiological classification of sympathetic neurons in the rat superior cervical ganglion. J. Neurophysiol. 95: 187-95, 2006.

Hahn, J., Kullman, P.H., Horn, J.P. and Levitan, E.S.  D2 Autoreceptors chronically enhance dopamine neuron activity. Journal of Neuroscience 26: 5240-5247, 2006.

Kullmann, P.H. and Horn, J.P. Excitatory muscarinic modulation strengthens virtual nicotinic synapses on sympathetic neurons and thereby enhances synaptic gain. J. Neurophysiol. Epub September 2006.