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

Elda Arrigoni, Donald G. Rainnie, Robert W. McCarley, Robert W. Greene

Research output: Contribution to journalArticle

61 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1076-1085
Number of pages10
JournalJournal of Neuroscience
Volume21
Issue number3
StatePublished - 2001

Fingerprint

Adenosine
Adenosine Kinase
Presynaptic Receptors
Adenosine A1 Receptors
Neurons
Diencephalon
Adenosine Deaminase
Arousal
varespladib methyl
Cholinergic Agents
Brain Stem
Glutamic Acid
Sleep

Keywords

  • A1 receptors
  • Adenosine
  • Adenosine kinase inhibitor
  • Electrophysiology
  • Evoked EPSC
  • Laterodorsal tegmental (LDT) nucleus
  • Sleep
  • Synaptic modulation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum. / Arrigoni, Elda; Rainnie, Donald G.; McCarley, Robert W.; Greene, Robert W.

In: Journal of Neuroscience, Vol. 21, No. 3, 2001, p. 1076-1085.

Research output: Contribution to journalArticle

Arrigoni, Elda ; Rainnie, Donald G. ; McCarley, Robert W. ; Greene, Robert W. / Adenosine-mediated presynaptic modulation of glutamatergic transmission in the laterodorsal tegmentum. In: Journal of Neuroscience. 2001 ; Vol. 21, No. 3. pp. 1076-1085.
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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.",
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AB - 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.

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