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Adenosine is considered to be a key regulator of sleep homeostasis by promoting slow-wavesleep through inhibition of the brain's arousal centers. However, little is known aboutthe effect of adenosine on neuronal network activity at the cellular level in theneocortex. Here, we show that adenosine differentially modulates synaptic transmissionbetween different types of neurons in cortical layer 4 (L4) through activation of pre-and/or postsynaptically located adenosine A1 receptors. In recurrent excitatoryconnections between L4 spiny neurons, adenosine suppresses synaptic transmission throughactivation of both pre- and postsynaptic A1 receptors. In reciprocal excitatory andinhibitory connections between L4 spiny neurons and interneurons, adenosine stronglysuppresses excitatory transmission via activating presynaptic A1 receptors but onlyslightly suppresses inhibitory transmission via activating postsynaptic A1 receptors.Adenosine has no effect on inhibitory transmission between L4 interneurons. The effect ofadenosine is concentration dependent and first visible at a concentration of 1 μM.The effect of adenosine is blocked by the specific A1 receptor antagonist,8-cyclopentyltheophylline or the nonspecific adenosine receptor antagonist, caffeine. Bydifferentially affecting excitatory and inhibitory synaptic transmission, adenosinechanges the excitation–inhibition balance and causes an overall shift to lowerexcitability in L4 primary somatosensory (barrel) cortical microcircuits.

Adenosine Differentially Modulates Synaptic Transmission of Excitatory and Inhibitory Microcircuits in Layer 4 of Rat Barrel Cortex