Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum

• Type of Material: Article
• Authors: Elda Arrigoni, Harvard University; Donald Rainnie, Emory University; Robert W. McCarley, Harvard University; Robert W. Greene, Harvard University
• Language: English
• Date: 2001-02-01
• Publisher: Society of Neuroscience
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2001 Society for Neuroscience
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1523/jneurosci.21-03-01076.2001
• Title of Journal or Parent Work: Journal of Neuroscience
• Volume: 21
• Issue: 3
• Start Page: 1076
• End Page: 1085
• Grant/Funding Information: E.A. was supported by the University of Milan, Italy and by SCOR Grant NHLBI-HL60292.; This work was supported by a Merit Award from The Department of Veterans Affairs to R.W.G., and by Specialized Center of Research (SCOR) Grant NHLBI-HL60292.
• Keywords: synaptic modulation; A1 receptors; Neurosciences; A(1) RECEPTOR; CALCIUM INFLUX; Neurosciences & Neurology; sleep; electrophysiology; SYNAPTIC TRANSMISSION; CENTRAL-NERVOUS-SYSTEM; Science & Technology; adenosine; BASAL FOREBRAIN; IN-VITRO; Life Sciences & Biomedicine; ENDOGENOUS ADENOSINE; PONTOMESENCEPHALIC TEGMENTUM; HIPPOCAMPAL PYRAMIDAL NEURONS; adenosine kinase inhibitor; evoked EPSC; laterodorsal tegmental (LDT) nucleus; RAT HIPPOCAMPUS
• Research Categories: Biology, Neuroscience

Abstract

The laterodorsal tegmentum (LDT) neurons supply most of the cholinergic tone to the brainstem and diencephalon necessary for physiological arousal. It is known that application of adenosine in the LDT nucleus increases sleep in vivo (Portas et al., 1997) and directly inhibits LDT neurons in vitro by activating postsynaptic adenosine A1 receptors (Rainnie et al., 1994). However, adenosine effects on synaptic inputs to LDT neurons has not been previously reported. We found that both evoked glutarnatergic EPSCs and GABAergic IPSCs were reduced by adenosine (50 μM). A presynaptic site of action for adenosine A1 receptors on glutamatergic afferents was suggested by the following: (1) adenosine did not affect exogenous glutamate-mediated current, (2) adenosine reduced glutamatergic miniature EPSC (mEPSC) frequency, without affecting the amplitude, and (3) inhibition of the evoked EPSC was mimicked by the A1 agonist N6-cyclohexyladenosine (100 nM) but not by the A2 agonist N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)-ethyl]-adenosine (10 nM). The A1 receptor antagonist 8-cyclopentyltheophylline (CPT; 200 nM) potentiated the evoked EPSCs, suggesting the presence of a tonic activation of presynaptic A1 receptors by endogenous adenosine. The adenosine kinase inhibitor, 5-iodotubercidin (10 μM), mimicked adenosine presynaptic and postsynaptic effects. These effects were antagonized by CPT or adenosine deaminase (0.8 IU/ml), suggesting mediation by increased extracellular endogenous adenosine. Together, these data suggest that the activity of LDT neurons is under inhibitory tone by endogenous adenosine through the activation of both presynaptic A1 receptors on excitatory terminals and postsynaptic A1 receptors. Furthermore, an alteration of adenosine kinase activity modifies the degree of this inhibitory tone.