A cholinoceptive desynchronized sleep induction zone in the anterodorsal pontine tegmentum: locus of the sensitive region

Abstract

Carbachol, a long-acting cholinergic agonist, was microinjected (4 micrograms/250 nl per 90 s) into 90 sites within the anterodorsal pontine tegmentum of four cats and the time to onset and percentage of time spent in a desynchronized sleep-like state during 40 min postinjection were calculated. Compared with more posteroventral pontine sites, the shorter latencies and higher percentages observed confirmed earlier predictions of a sensitive cholinoceptive zone in the anterodorsal pons. In 27 trials a desynchronized sleep-like state was observed within 5 min; in 31 trials the latency was 5-10 min and in the remaining 32 trials, greater than 10 min. Plotting the desynchronized sleep-like state latency and the desynchronized sleep-like state percentage as a function of the three-dimensional coordinates revealed that injection sites with short latency (less than 5 min) and high percentage (greater than 80%) were concentrated between the coordinates of P 1.0 to 3.5 and V -3.5 to -5.5, at the lateral coordinate L 2.0. On the frontal plane, the short desynchronized sleep-like state latency and high desynchronized sleep-like state percentage sites begin in the pontine tegmental region just lateral to the ventral tegmental nucleus and extend 3 mm ventrocaudally. A regression plot of the data in sagittal plane 2.0 revealed a short latency axis, around which the short latency sites cluster, running in a slightly dorsoventral direction from about P 1.0 to V -4.0 to P 4.0 to V -5.5. This observation suggests that the sensitive zone might approximate a cylinder in shape, a hypothesis supported by the correlation of longer latencies and lower percentages at increasing radial distance from the axis. The non-linear relationship between cholinergic potency and distance from the short latency axis suggests that the desynchronized sleep-like state latency is a function of two factors; a variable diffusion-based delay of carbachol to distant neuronal populations involved in the desynchronized sleep-like state production, and a fixed recruitment-based delay following activation of neurons in the sensitive zone. Interpretation of these findings in light of earlier studies involving microstimulation of the pontine tegmentum argue in favor of a distributed network of discrete neuronal populations as the source of desynchronized sleep generation.