Immunoregulation of Synaptic Plasticity, Chemoreception and Excitable Membranes
Our research goal is to understand how the immune and nervous systems communicate with each other at the cellular level. Interaction of antigen with mast cell-bound antibodies and the consequent release of inflammatory mediators are pivotal events in immediate hypersensitivity reactions (anaphylactoid responses).
Associated with immediate hypersensitivity reactions is an increase in nervous activity within the sensory and the autonomic nervous systems. Using convergent cellular electrophysiological, optical and immunological techniques, we are studying how neuronal membrane excitability and synaptic transmission is altered by inflammatory mediators released from allergen-activated mast cells in vitro and in vivo. Our laboratory is currently pursuing two avenues of research.
In one, we are examining whether pre- or post-synaptic membrane properties contribute to antigen-induced long-term (hrs) potentiation (A-LTP) of synaptic neurotransmission within sympathetic ganglia. The nature of the signal molecule(s) elaborated by mast cell activation is also being sought. In some of these studies we use normal and mast cell-deficient mice to discern whether cells other than mast cells contribute to antigen-induced changes in synaptic transmission. In an other area we combine fluorescent retrograde neuronal labelling techniques with standard intracellular recording methods to examine how specific antigen challenge of mast cells housed in vagal sensory ganglia alters the excitability and chemosensitivity of airway-specific vagal afferents in vitro. To quantify cellular mechanisms responsible for antigen-induced changes we employ flash photolysis techniques to activate a variety of 'caged' reagents introduced into vagal sensory cell bodies by micropettes in conjunction with standard current and voltage clamp recording methods. Often membrane current and voltage recordings are made simultaneously with fluorescence imaging of intracellular calcium.
Lab Techniques and Equipment:
Techniques: Current and voltage clamp recording Fluroresence measurements of intracellular ions Neuronal tracing with fluroresence markers Caged second messengers Cell culture Active and passive immunization Immunocytochemistry
• B.S., Bethany College, W. Va.
• Ph.D., University of Utah (Pharmacology)
• Postdoctoral training, Neuroscience Department, Beckmann Research Institute, City of Hope National Medical Center, Durate, California
Dr. Ruth Cordora-Rodriguez (1997- )
Dr. Liz Katz (1999- )
Eric Lancaster (MD/PhD student): Neuroscience Program
Tony Glover (PhD student): Neuroscience Program
Eun Joo Oh, MD (PhD student): Pharmacology Program
Weinreich, D., Undem, B. J., Taylor, G. and Barry, M. F. Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig. J. Neurophysiol., 73: 2004-2016, 1995.
Jafri, M. S. and Weinreich, D. Substance P hyperpolarizes vagal sensory neurones of the ferret. J. Physiol. 493: 157-166, 1996.
Albuquerque, A. A. C., Leal-Cardoso, J. H. and Weinreich, D. Antigen-induced synaptic plasticity in sympathetic ganglia from actively and passively sensitized guinea pigs J. Autono. Ner. Sys. 61: 139-144, 1996
Moore, K. A., Taylor, G. E. & Weinreich, D. Serotonin unmasks functional NK-2 receptors In vagal sensory neurones of the guinea pig. J. Physiol. , 514: 111-124, 1999.
Moore, K. A., Undem, B. J. & Weinreich, D. Anitgen inhalation unmasks NK-2 tachykinin receptor-mediated responses in vagal afferents. Am J Respir Crit Care Med (in press).
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