title: GABA signaling in the nucleus tractus solitarius sets the level of activity in dorsal motor nucleus of the vagus cholinergic neurons in the vagovagal circuit.
abstract: It has been proposed that there is an "apparent monosynaptic" connection between gastric vagal afferent nerve terminals and inhibitory projection neurons in the nucleus tractus solitarius (NTS) and that two efferent parallel pathways from the dorsal motor nucleus of the vagus (DMV) influence peripheral organs associated with these reflexes (6). The purpose of our study was to verify the validity of these views as they relate to basal control of gastric motility. To test the validity of a direct connection of vagal afferent terminals (known to release l-glutamate) directly impacting second-order projection neurons, we evaluated the effect of GABA(A) receptor blockade in the area of the medial subnucleus of the tractus solitarius (mNTS) on gastric motility. Microinjection of bicuculline methiodide into the mNTS produced robust decreases in gastric motility (-1.6 +/- 0.2 mmHg, P < 0.05, n = 23), which were prevented by cervical vagotomy and by pretreatment with kynurenic acid microinjected into the mNTS. Kynurenic acid per se had no effect on gastric motility. However, after GABA(A) receptor blockade in the mNTS, kynurenic acid produced a robust increase in gastric motility. To test for the contribution of two parallel efferent DMV pathways, we assessed the effect of either intravenous atropine methylbromide or N(G)-nitro-l-arginine methyl ester on baseline motility and on decreases in gastric motility induced by GABA(A) receptor blockade in the mNTS. Only atropine methylbromide altered baseline motility and prevented the effects of GABA(A) receptor blockade on gastric motility. Our data demonstrate the presence of intra-NTS GABAergic signaling between the vagal afferent nerve terminals and inhibitory projection neurons in the NTS and that the cholinergic-cholinergic excitatory pathway comprises the functionally relevant efferent arm of the vagovagal circuit.
authors.affiliation: Interdisciplinary Program in Neuroscience, Georgetown Univ. Medical Center, 3900 Reservoir Rd., NW, Washington, DC 20057, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Herman
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Cruz
authors.forename: Niaz
authors.initials: N
authors.lastname: Sahibzada
authors.forename: Joseph
authors.initials: J
authors.lastname: Verbalis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gillis
mesh_terms: D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D058787:GABA-A Receptor Antagonists; D005769:Gastrointestinal Motility / Q000187:drug effects; D007736:Kynurenic Acid / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D023421:Models, Animal; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D015203:Reproducibility of Results; D017552:Solitary Nucleus / Q000187:drug effects / Q000378:metabolism*; D013270:Stomach / Q000294:innervation*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001286:Atropine Derivatives; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D018727:Muscarinic Antagonists; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; C006649:methylatropine; D007736:Kynurenic Acid; D001640:Bicuculline