Figure 4.

Summary of results and model of how adenosine may promote sleep in the basal forebrain (BF). BF cholinergic and GABAergic/PV neurons project to the cortex and promote cortical activation through their effects on cortical pyramidal neurons and GABAergic interneurons. During prolonged wakefulness extracellular adenosine levels rise due to transport of adenosine by plasma membrane transporters (not shown) or due to degradation of ATP released from glia or as a co-transmitter. Adenosine inhibits cortically projecting BF cholinergic and GABAergic neurons by inhibiting their local glutamatergic inputs through activation of A1 receptors, thus promoting sleep. Adenosine also inhibits the glutamate release from the axon terminals to cholinergic neurons, which could be from either local or distant glutamatergic neurons. Some local GABAergic neurons sending projections to small I_h GABAergic neurons are also sensitive to adenosine. ACh⁺, cholinergic ATP, adenosine triphosphate.