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The Journal of Neuroscience, March 11, 2009, 29(10):3093-3102; doi:10.1523/JNEUROSCI.2648-08.2009

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Behavioral/Systems/Cognitive
Chronic Sustained Hypoxia Enhances Both Evoked EPSCs and Norepinephrine Inhibition of Glutamatergic Afferent Inputs in the Nucleus of the Solitary Tract

Weirong Zhang, Flávia R. Carreño, J. Thomas Cunningham, and Steve W. Mifflin

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900

Correspondence should be addressed to Dr. Steve W. Mifflin, Department of Pharmacology, MSC 7764, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Email: mifflin{at}uthscsa.edu

The nucleus of the solitary tract (NTS) receives inputs from both arterial chemoreceptors and central noradrenergic neural structures activated during hypoxia. We investigated norepinephrine (NE) modulation of chemoreceptor afferent integration after a chronic exposure to sustained hypoxia (CSH) (7–8 d at 10% FIO₂). Whole-cell recordings of NTS second-order neurons identified by DiA (1,1'-dilinoleyl-3,3,3',3'-tetra-methylindocarbocyanine, 4-chlorobenzenesulphonate) labeling of carotid bodies were obtained in a brain slice. Electrical stimulation of the solitary tract was used to evoke EPSCs. CSH exposure increased evoked EPSC (eEPSC) amplitude via both presynaptic and postsynaptic mechanisms. NE dose dependently decreased the amplitude of eEPSCs. NE increased the paired-pulse ratio of eEPSCs and reduced the frequency of miniature EPSCs, suggesting a presynaptic mechanism. EC₅₀ of NE inhibition of eEPSCs was lower in CSH cells (3.0 ± 0.9 µM; n = 5) than in normoxic (NORM) cells (7.6 ± 1.0 µM; n = 7; p < 0.01). NE (10 µM) elicited greater inhibition of eEPSCs in CSH cells (63 ± 2%; n = 16) than NORM cells (45 ± 3%; n = 21; p < 0.01). The -adrenoreceptor antagonist phentolamine abolished NE inhibition of eEPSCs. CSH enhanced the 2-adrenoreceptor agonist clonidine-mediated inhibition (3 µM; NORM, 23 ± 2%, n = 5 vs CSH, 44 ± 5%, n = 4; p < 0.05) but attenuated 1-adrenoreceptor agonist phenylephrine-mediated inhibition (40 µM; NORM, 36 ± 2%, n = 11 vs CSH, 26 ± 4%, n = 6; p < 0.05). The 2-adrenoreceptor antagonist yohimbine abolished CSH-induced enhancement of NE inhibition of eEPSCs. These results demonstrate that CSH increases evoked excitatory inputs to NTS neurons receiving arterial chemoreceptor inputs. CSH also enhances NE inhibition of glutamate release from inputs to these neurons via presynaptic 2-adrenoreceptors. These changes represent central neural adaptations to CSH.

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Received June 10, 2008; revised Jan. 21, 2009; accepted Feb. 2, 2009.

Correspondence should be addressed to Dr. Steve W. Mifflin, Department of Pharmacology, MSC 7764, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900. Email: mifflin{at}uthscsa.edu

This article has been cited by other articles:

				S. J. McDougall, J. H. Peters, and M. C. Andresen Convergence of Cranial Visceral Afferents within the Solitary Tract Nucleus J. Neurosci., October 14, 2009; 29(41): 12886 - 12895. [Abstract] [Full Text] [PDF]

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