Home > Conscious > Chapter 7 > 7.4. The Role of Adenosine in Sleep


The astrocytes can obstruct synaptic transmission via adenosine. During wakefulness, the intense activities of glutamatergic neurons release a large amount of glutamate, which may activate mGluR and NMDA receptor on astrocyte's cell membrane to stimulate Ca2+-dependent release of ATP (Figure 5-6). The released ATP will break down into adenosine. Hence, the extracellular fluid will accumulate more and more adenosine, which can act on its A1 receptor to open GIRK channels (Chapter 6), inhibit neuronal firing and consequently reduce glutamate release (Bjorness and Greene, 2009) (Figure 7-6).


Figure 7-6. Adenosine may act on its A1 receptor to open GIRK channels, thereby reducing glutamate release.

The reduction of glutamate release should attenuate global excitability, including neurons that oscillate at the α band. According to the Alpha Hypothesis proposed in Section 5.4, this should impair the clarity of consciousness. Thus, after a long busy day, our consciousness will begin to blur in the midnight, feeling sleepy. This sleep pressure is mainly caused by adenosine. The reason why caffeine can promote wakefulness is because it acts as an antagonist of adenosine receptors (Ribeiro and Sebastiao, 2010).

In addition to the inhibition of glutamate release, adenosine can also exert more powerful effects on sleep by activating the GABA neurons in ventrolateral preoptic nucleus (VLPO). VLPO contains a population of GABA neurons that can directly inhibit neuronal firing in the ascending arousal system. These GABA neurons are inhibited by another population of GABA neurons (called interneurons) during wakefulness. Adenosine can open GIRK channels to inhibit the GABA interneurons, thus activating the GABA neuron that directly inhibit the arousal system. This process is known as "disinhibition" (Chamberlin et al, 2003; Morairty et al, 2004).


Figure 7-7. Adenosine can activate VLPO which, in turn, suppresses the arousal system. All neurotransmitters in this figure may have varying degrees of effects on ACC alpha rhythms, but orexin seems to contribute the most, as deficient orexin transmission is sufficient to produce narcolepsy (De la Herrán-Arita et al., 2011). Inhibition of dopaminergic neurons in vPAG reduces the activation of D1 receptors in layer V cortex, thus facilitating slow wave sleep (Section 7.6).