9601165 Leonard Synaptic and non-synaptic interactions between mesopontine cholinergic neurons controlling REM sleep. An important step toward understanding how we sleep and dream has been the identification of specific groups of neurons in the brain that generate these states. An important next step will be to determine how these neurons interact. This proposed work is focused on how signals from neurons that trigger dreaming and waking are controlled. These cells, which use the chemical acetylcholine to communicate with their distant target-cells, may also release this chemical locally to regulate their own activity. Our experiments will test this possibility by stimulating these cells and determining if any released acetylcholine can influence the neurons in the immediate neighborhood of the stimulated cells. We will also use a novel method to visualize these neurons with the electron microscope to look for possible chemical release sites. This will allow us to determine if these release sites make direct contact with neighboring neurons that contain acetylcholine or are positioned at a distance from these neurons and their processes. The results will help determine if acetylcholine acts as a local feedback signal and whether this signal gets transmitted via classical rapid cell-to- cell contacts or via a slower and longer pathway through the extracellular space. Since these two signaling paths have different spatial and temporal properties, our results will make testable predictions about the role of acetylcholine in controlling the timing of sleep and wakefulness. Accordingly, these findings will advance our understanding of the neural mechanisms of sleeping and dreaming.
