title: Carbachol excites sublaterodorsal nucleus neurons projecting to the spinal cord.
abstract: Considerable electrophysiological and pharmacological evidence has long suggested an important role for acetylcholine in the regulation of rapid-eye-movement (REM) sleep. For example, injection of the cholinergic agonist carbachol into the dorsomedial pons produces an REM sleep-like state with muscle atonia and cortical activation, both of which are cardinal features of REM sleep. Located within this region of the pons is the sublaterodorsal nucleus (SLD), a structure thought to be both necessary and sufficient for generating REM sleep muscle atonia. Subsets of glutamatergic SLD neurons potently contribute to motor inhibition during REM sleep through descending projections to motor-related glycinergic/GABAergic neurons in the spinal cord and ventromedial medulla. Prior electrophysiological and pharmacological studies examining the effects of acetylcholine on SLD neurons have, however, produced conflicting results. In the present study, we sought to clarify how acetylcholine influences the activity of spinally projecting SLD (SLDsp) neurons. We used retrograde tracing in combination with patch-clamp recordings and recorded pre- and postsynaptic effects of carbachol on SLDsp neurons. Carbachol acted presynaptically by increasing the frequency of glutamatergic miniature excitatory postsynaptic currents. We also found that carbachol directly excited SLDsp neurons by activating an Na(+)-Ca(2+) exchanger. Both pre- and postsynaptic effects were mediated by co-activation of M1 and M3 muscarinic receptors. These observations suggest that acetylcholine produces synergistic, excitatory pre- and postsynaptic responses on SLDsp neurons that, in turn, probably serve to promote muscle atonia during REM sleep.
authors.affiliation: Department of Neurology, Beth Israel Deaconess Medical Center, 3 Blackfan Circle, Center for Life Science Room 713, Boston, MA 02215, USA.    earrigon@bidmc.harvard.edu.
authors.forename: F J
authors.initials: FJ
authors.lastname: Weng
authors.forename: R H
authors.initials: RH
authors.lastname: Williams
authors.forename: J M
authors.initials: JM
authors.lastname: Hawryluk
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: T E
authors.initials: TE
authors.lastname: Scammell
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
authors.forename: E
authors.initials: E
authors.lastname: Arrigoni
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D011149:Pons / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D019831:Sodium-Calcium Exchanger / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D018721:Muscarinic Agonists; D043643:Receptor, Muscarinic M1; D043587:Receptor, Muscarinic M3; D019831:Sodium-Calcium Exchanger; D018698:Glutamic Acid; D002217:Carbachol; D000109:Acetylcholine