E. Arrigoni et al., Adenosine-mediated presynaptic modulation of glutamatergic transmission inthe laterodorsal tegmentum, J NEUROSC, 21(3), 2001, pp. 1076-1085
The laterodorsal tegmentum (LDT) neurons supply most of the cholinergic ton
e 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 A(1) receptors (Rainnie et al., 1994). H
owever, adenosine effects on synaptic inputs to LDT neurons has not been pr
eviously reported. We found that both evoked glutamatergic EPSCs and GABAer
gic IPSCs were reduced by adenosine (50 muM). A presynaptic site of action
for adenosine A(1) receptors on glutamatergic afferents was suggested by th
e following: (1) adenosine did not affect exogenous glutamate-mediated curr
ent, (2) adenosine reduced glutamatergic miniature EPSC (mEPSC) frequency,
without affecting the amplitude, and (3) inhibition of the evoked EPSC was
mimicked by the A(1) agonist N6-cyclohexyladenosine (100 nM) but not by the
A(2) agonist N6-[2-(3,5-dimethoxyphenyl)-2-(methylphenyl)-ethyl]-adenosine
(10 nM).
The A(1) receptor antagonist 8-cyclopentyltheophylline (CPT; 200 nM) potent
iated the evoked EPSCs, suggesting the presence of a tonic activation of pr
esynaptic A(1) receptors by endogenous adenosine. The adenosine kinase inhi
bitor, 5-iodotubercidin (10 muM), mimicked adenosine presynaptic and postsy
naptic effects. These effects were antagonized by CPT or adenosine deaminas
e (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 bo
th presynaptic A(1) receptors on excitatory terminals and postsynaptic A(1)
receptors. Furthermore, an alteration of adenosine kinase activity modifie
s the degree of this inhibitory tone.