title: Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function.
abstract: The nucleus tractus solitarii (nTS) is the initial central termination site for visceral afferents and is important for modulation and integration of multiple reflexes including cardiorespiratory reflexes. Glutamate is the primary excitatory neurotransmitter in the nTS and is removed from the extracellular milieu by excitatory amino acid transporters (EAATs). The goal of this study was to elucidate the role of EAATs in the nTS on basal synaptic and neuronal function and cardiorespiratory regulation. The majority of glutamate clearance in the central nervous system is believed to be mediated by astrocytic EAAT 1 and 2. We confirmed the presence of EAAT 1 and 2 within the nTS and their colocalization with astrocytic markers. EAAT blockade withdl-threo-β-benzyloxyaspartic acid (TBOA) produced a concentration-related depolarization, increased spontaneous excitatory postsynaptic current (EPSC) frequency, and enhanced action potential discharge in nTS neurons. Solitary tract-evoked EPSCs were significantly reduced by EAAT blockade. Microinjection of TBOA into the nTS of anesthetized rats induced apneic, sympathoinhibitory, depressor, and bradycardic responses. These effects mimicked the response to microinjection of exogenous glutamate, and glutamate responses were enhanced by EAAT blockade. Together these data indicate that EAATs tonically restrain nTS excitability to modulate cardiorespiratory function.
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.
authors.forename: Michael P
authors.identifier: http://orcid.org/0000-0002-7883-4473
authors.initials: MP
authors.lastname: Matott
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.
authors.forename: Brian C
authors.identifier: http://orcid.org/0000-0001-8507-8218
authors.initials: BC
authors.lastname: Ruyle
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri; and Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri.
authors.forename: Eileen M
authors.identifier: http://orcid.org/0000-0003-4552-1021
authors.initials: EM
authors.lastname: Hasser
authors.affiliation: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri, Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri klinedd@missouri.edu.
authors.forename: David D
authors.identifier: http://orcid.org/0000-0003-3269-0184
authors.initials: DD
authors.lastname: Kline
mesh_terms: D000200:Action Potentials; D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D050491:Glutamate Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006339:Heart Rate; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D017552:Solitary Nucleus / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid
keywords: astrocytes; glutamate transporters; phrenic nerve activity; sympathetic nervous system; synaptic currents