Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

Abstract

Prostaglandin E 2 (PGE 2 ) is a prototypical inflammatory mediator that excites and sensitizes cell bodies (Kwong and Lee, 2002; and peripheral nerve terminals (Ho et al. 2000) of primary vagal sensory neurons. Nearly all central nerve terminals of vagal afferents are in the nucleus tractus solitarius (NTS), where they operate with a high probability of release (Doyle and Andresen, 2001). We studied the effect of PGE 2 on synaptic transmission between tractus solitarius afferent nerve terminals and the second order NTS neurons in brain stem slices of Sprague Dawley rats. Whole-cell patch recording in voltage clamp mode was used to study evoked excitatory postsynaptic glutamatergic currents (evEPSCs) from NTS neurons elicited by electrical stimulation of the solitary tract (ST). In 34 neurons, bath applied PGE 2 (200 nM) decreased the evEPSC amplitude by 49 ± 5 %. In 22 neurons, however, PGE 2 had no effect. We also tested 15 NTS neurons for capsaicin sensitivity. Seven neurons generated evEPSCs that were equally unaffected by PGE 2 and capsaicin. Conversely, evEPSCs of the other 8 neurons, which were PGE 2 -responsive, were abolished by 200 nM capsaicin. Furthermore, the PGE 2-induced depression of evEPSCs was associated with an increase in the paired pulse ratio and a decrease in both the frequency and amplitude of the spontaneous excitatory postsynaptic currents (sEPSCs) and TTX-independent spontaneous miniature excitatory postsynaptic currents (mEPSCs). These results suggest that PGE 2 acts both presynaptically on nerve terminals and postsynaptically on NTS neurons to reduce glutamatergic responses. KeywordsGlutamate; AMPA receptors; Presynaptic; Postsynaptic Many neurons in the nucleus of the tractus solitarius (NTS) receive nerve terminals whose axons arise from cell bodies of vagal primary afferent neurons located in the nodose and jugular vagal ganglia. These primary vagal afferents convey diverse sensory information from a variety of receptors located in cardiovascular, respiratory, gastrointestinal and other organs to the NTS neurons in the medulla (Contreras, 1982). Thus, the first monosynaptic contact for myelinated A-type and unmyelinated C-type axons of primary vagal afferent fibers are the second-order neurons in the NTS. These fibers reach second-order NTS neurons via the solitary tract (Doyle Corresponding author: Nora Laaris, Department Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, 655 W. Baltimore Street, Baltimore, MD 21201, Tel: (410) 706-1409, Fax: (410) 706-0032, e-mail: nlaar001@umaryland.edu. Section Editor: Dr. Yoland Smith, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its fin...

Sensory afferent and hypoxia-mediated activation of nucleus tractus solitarius neurons that project to the rostral ventrolateral medulla

“…We specifically tested monosynaptic RVLM-projecting cells, and found that bath application of the non-NMDA receptor antagonist CNQX abolished TS evoked EPSCs and sEPSCs. Thus, similar to CVLM-projecting nTS neurons (Bailey et al, 2006; Li and Yang, 2007) and other second-order nTS cells (Chen et al, 1999; Doyle and Andresen, 2001; Kline et al, 2002; Laaris and Weinreich, 2007), non-NMDA receptors appear to mediate the majority of excitatory inputs to RVLM-projecting nTS cells.…”

Administration of IL-1β to the 4th ventricle causes anorexia that is blocked by agouti-related peptide and that coincides with activation of tyrosine-hydroxylase neurons in the nucleus of the solitary tract

“…Alternate means of IL-1β activation of TH neurons include relayed messages from other neurons or glial cells. Other researchers have recently shown that exposure to PGE 2 —a downstream product of IL-1β stimulation in glial cells—modulated neuronal electrical activity in the NTS, suggesting that glial cell production of PGE 2 in response to IL-1β may be the means by which TH neurons are activated [19,26]. Further experiments will be required to investigate whether TH neurons are activated by PGE 2 .…”

Plasticity in glutamatergic NTS neurotransmission

“…Angiotensin II (Barnes et al, 2003), substance P (Sekizawa et al, 2003; Bailey et al, 2004), enkephalins (Glatzer and Smith, 2005), adenosine/ATP (Kato and Shigetomi, 2001; Shigetomi and Kato, 2004), prostaglandin E2 (Laaris and Weinreich, 2007) and norepinepherine (Zhang and Mifflin, 2007) alter neurotransmitter release, postsynaptic activity, or the magnitude of synaptic depression. Dopamine also reduces TS-evoked glutamate release to induce synaptic depression in the NTS (Kline et al, 2002).…”