Phone: (412) 648-9429
Fax: (412) 648-1441
Email: jph@pitt.edu

Ph.D., University of Miami

Research Interests

Dr. Horn's research examines how synaptic interactions regulate information processing in autonomic ganglia. In this system, the wiring of connections is simple and yet the circuit contains a rich diversity of synaptic mechanisms mediated by ionotropic and metabotropic receptors. Most basic is the presynaptic release of acetylcholine, which transmits fast synaptic excitation through nicotinic receptors. In addition, multiple forms of slow synaptic modulation arise through muscarinic receptors and other receptor systems. We have exploited the relatively simple organization of this circuit to investigate fundamental rules that govern the slow metabotropic modulation of fast ionotropic synapses. The approach combines cellular neurophysiology together with computational modeling and anatomy. Based on experimental observations, a general theory of ganglionic integration has been developed and used to construct computational simulations with a conductance-based neuronal model. Results from this approach lead to the general prediction that autonomic ganglia can function as variable synaptic amplifiers of neuronal activity. In this framework, convergent 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 by altering the strength or 'wieghts' of nicotinic synapses. These ideas are currently being tested in experiments that employ the dynamic-clamp method to place virtual nicotinic synapses on living neurons with a computer. In this way it becomes possible to understand how multiple converging synapses, of defined strength and activity, interact with one another and with modulatory mechanisms. Work in the Horn lab embraces the CNBC mission in three key ways. First, the autonomic system is essential for generation of motivated and emotionally driven behaviors. Second, the cholinergic signaling mechanisms that operate in ganglia also regulate circuit function in the thalamus and cerebral cortex. Drugs and diseases that alter central cholinergic function produce profound changes in cognition. Third, the cellular and molecular approach developed to analyze simple ganglionic circuits can also act as a model for studying more complex circuits in the forebrain and for understanding other systems that employ sensory feedback to control motor outputs. Students and postdoctoral fellows in the Horn lab have opportunities to master a multi-disciplinary approach to neural circuit analysis from the bottom up.

Recent Publications

• Kullmann, PH, Wheeler DW, Beacom J, Horn JP: Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT. J Neurophysiol 91: 542-554, 2004.
• Wheeler DW, Kullmann DW, Horn JP: Estimating use-dependent synaptic gain in auotonomic ganglia by computational simulation and dynamic-clamp analysis. J Neurophysiol 92(5): 2659-71. 2004.
• Karila P, Horn JP: Secondary nicotinic synapses on sympathetic B neurons and their putative role in ganglionic amplification of activity. J Neurosci 20: 908-918, 2000.
• Schobesberger H, Wheeler DW, Horn JP: A model for pleiotropic muscarinic potentiation of fast synaptic transmission. J Neurophysiol 83: 1912-1923, 2000.