Excitatory amino acid transporters tonically restrain nTS synaptic and neuronal activity to modulate cardiorespiratory function

• Published in: Journal of neurophysiology Vol. 115; no. 3; pp. 1691 - 1702
• Main Authors: Matott, Michael P., Ruyle, Brian C., Hasser, Eileen M., Kline, David D.
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.03.2016
• Series: Glial Cells and Neuronal Signaling
• Subjects: Action Potentials; Animals; Call for Papers; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials; Glutamate Plasma Membrane Transport Proteins - antagonists & inhibitors; Glutamate Plasma Membrane Transport Proteins - metabolism; Glutamic Acid - metabolism; Heart Rate; Male; Neurons - metabolism; Neurons - physiology; Rats; Rats, Sprague-Dawley; Respiration; Solitary Nucleus - metabolism; Solitary Nucleus - physiology; Synapses - drug effects; Synapses - metabolism; Synapses - physiology; phrenic nerve activity; synaptic currents; astrocytes; glutamate transporters; sympathetic nervous system
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01054.2015

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 with dl- 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.