title: GABAA receptors are located in cholinergic terminals in the nucleus pontis oralis of the rat: implications for REM sleep control.
abstract: The oral pontine reticular formation (PnO) of rat is one region identified in the brainstem as a rapid eye movement (REM) sleep induction zone. Microinjection of GABA(A) receptor antagonists into PnO induces a long lasting increase in REM sleep, which is similar to that produced by cholinergic agonists. We previously showed that this REM sleep-induction can be completely blocked by a muscarinic antagonist, indicating that the REM sleep-inducing effect of GABA(A) receptor antagonism is dependent upon the local cholinergic system. Consistent with these findings, it has been reported that GABA(A) receptor antagonists microdialyzed into PnO resulted in increased levels of acetylcholine. We hypothesize that GABA(A) receptors located on cholinergic boutons in the PnO are responsible for the REM sleep induction by GABA(A) receptor antagonists through blocking GABA inhibition of acetylcholine release. Cholinergic, varicose axon fibers were studied in the PnO by immunofluorescence and confocal, laser scanning microscopy. Immunoreactive cholinergic boutons were found to be colocalized with GABA(A) receptor subunit protein γ2. This finding implicates a specific subtype and location of GABA(A) receptors in PnO of rat in the control of REM sleep.
authors.affiliation: Department of Veterans Affairs, North Texas Health Care System, Dallas, TX 75216, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Chang-Lin
authors.initials: CL
authors.lastname: Liang
authors.affiliation: Department of Veterans Affairs, North Texas Health Care System, Dallas, TX 75216, USA; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: gerald.marks@utsouthwestern.edu.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Marks
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002799:Cholinergic Fibers / Q000378:metabolism; D059329:Cholinergic Neurons / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D011963:Receptors, GABA-A / Q000378:metabolism*; D012154:Reticular Formation / Q000166:cytology* / Q000187:drug effects; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; C493461:Slc18a3 protein, rat; C118623:Slc32a1 protein, rat; D050494:Vesicular Acetylcholine Transport Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D000123:Acetyltransferases; C071107:microtubule-associated protein acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: ACh; BZ; GABA(A) receptor subunit; GABA(A)R; GAD67; Immunohistochemistry; KCC2; Laser scanning confocal microscopy; MAP2; PB; PnO; Pontine reticular formation; REM; REM sleep induction zone; VAChT; VGAT; Vesicular transporter; acetylcholine; benzodiazepine; glutamic acid decarboxylase-67; microtubule-associated protein 2; oral pontine reticular formation; phosphate buffer; potassium-chloride cotransporter-2; rapid eye movement; type-A GABA receptor; vesicular GABA transporter; vesicular acetylcholine transporter