k John P Horn
Department of Neurobiology

Horn, John P.
Professor, Neurobiology, Associate Dean of Graduate Studies
Ph.D., University of Miami (1979)
Address: E1458 BSTWR
   200 Lothrop Street
   Pittsburgh, PA 15213-2536
Telephone: 412-648-9429
Fax: 412-648-1441
E-mail: jph@pitt.edu
Website: http://hornlab.neurobio.pitt.edu
see also: Interdisciplinary Biomedical Graduate Program

Synaptic Computation and Neuromodulation in Catecholaminergic Neurons

We study the electrophysiology of noradrenergic sympathetic neurons and dopamine neurons in the substantia nigra. These neurons are implicated in a wide range of human pathologies ranging from hypertension and post-traumatic stress disorder to Parkinson’s disease, drug addiction, learning disorders and schizophrenia. However, the questions we ask are much more basic. Rather than focus upon disease models, we combine electrophysiology with computational approaches to identify the cellular and molecular origins of synaptic integration and neuromodulation in the context of circuit function.

As an example, our recent work on integration in sympathetic neurons shows how they can function as synaptic amplifiers whose gain may be regulated by excitatory muscarinic modulation. This is potentially important for a couple of reasons. First, these cells are embedded in negative feedback loops whose ability to control cardiovascular function depends critically on gain. Our work therefore identifies a synaptic mechanism of amplification that may serve to enhance homeostatic blood pressure control. Second, the type of muscarinic excitation found in sympathetic neurons also operates in the cerebral cortex, where it influences memory and is a drug target in Alzheimer’s disease.

Other recent work from our lab has focused on the pacemaker properties of dopamine neurons using brain slice preparations. This project is a collaboration with my colleague Ed Levitan in the Pharmacology Department, something very typical of our CNUP community. The thing that ties this project to the work on sympathetic neurons is a technique called dynamic clamp. With it one can implement virtual ion channels in cells using computer feedback. In our most recent project on dopamine neurons using the dynamic clamp we have studied the role of L-type calcium channels in pacemaking. Others in the field have argued that calcium entering through the L channels is essential. We have shown that after blocking the L channels with a drug that has been suggested as a potential treatment in Parkinson’s disease, one can restore pacemaking. This provides some of the best available evidence that L channels support pacing and it also proves that calcium entry is secondary, since virtual L type currents are not carried by calcium.

Students and Postdocs in the Horn lab have opportunities to learn electrophysiology from the bottom up and to combine it with computational modeling, neuroanatomy and molecular biology.

Sample Publications:

see also publications on the Horn Lab website

Weak and straddling secondary nicotinic synapses can drive firing in rat sympathetic neurons and thereby contribute to ganglionic amplification.
Rimmer K, Horn JP.
Front Neurol. 2010 Sep 23;1:130.

Vasomotor sympathetic neurons are more excitable than secretomotor sympathetic neurons in bullfrog paravertebral ganglia.
Kullmann PH, Horn JP.
Auton Neurosci. 2010 Jun 24;155(1-2):19-24.

Homeostatic regulation of M-current modulates synaptic integration in secretomotor, but not vasomotor, sympathetic neurons in the bullfrog.
Kullmann PH, Horn JP.
J Physiol. 2010 Mar 15;588(Pt 6):923-38.

CaV1.3 channel voltage dependence, not Ca2+ selectivity, drives pacemaker activity and amplifies bursts in nigral dopamine neurons.
Putzier I, Kullmann PHM, Horn JP, Levitan ES.
J Neurosci. 2009 Dec 9;29(49):15414-9.

Dopamine neuron responses depend exponentially on pacemaker interval.
Putzier I, Kullmann PH, Horn JP, Levitan ES.
J Neurophysiol. 2009 Feb;101(2):926-33.

Differential inhibition of Ca2+ channels by α2-adrenoceptors in three functional subclasses of rat sympathetic neurons.
Li C, and Horn JP.
J Neurophysiol. 2008 Dec;100(6):3055-63.

Excitatory muscarinic modulation strengthens virtual nicotinic synapses on sympathetic neurons and thereby enhances synaptic gain.
Kullmann, PHM & JP Horn.
J Neurophysiol. 2006 Dec;96(6):3104-13.

D2 autoreceptors chronically enhance dopamine neuron pacemaker activity.
Hahn J, Kullmann PHM, Horn JP, and ES Levitan.
J Neurosci. 2006 May 10;26(19):5240-7.

Physiological classification of sympathetic neurons in the rat superior cervical ganglion.
Li C, Horn JP.
J Neurophysiol. 2006 Jan;95(1):187-95.

PubMed Search for "Horn JP"

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