title: 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.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA 02115.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: A N
authors.initials: AN
authors.lastname: Mamelak
authors.forename: J J
authors.initials: JJ
authors.lastname: Quattrochi
authors.forename: J A
authors.initials: JA
authors.lastname: Hobson
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats; D004569:Electroencephalography / Q000187:drug effects; D005829:Geniculate Bodies / Q000502:physiology; D008297:Male; D008845:Microinjections; D009778:Occipital Lobe / Q000502:physiology; D011149:Pons / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012890:Sleep / Q000187:drug effects*
chemical_list: D002217:Carbachol