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Vagal afferent fibres determine the oxytocin‐induced modulation of gastric tone
Author(s) -
Holmes Gregory M.,
Browning Kirsteen N.,
Babic Tanja,
Fortna Samuel R.,
Coleman F. Holly,
Travagli R. Alberto
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.253732
Subject(s) - vagus nerve , oxytocin , area postrema , dorsal motor nucleus , brainstem , metabotropic glutamate receptor , solitary nucleus , chemistry , neuroscience , glutamatergic , glutamate receptor , cholinergic , efferent , medicine , endocrinology , biology , central nervous system , receptor , stimulation , afferent
Key points• Oxytocin (OXT) inputs to the brainstem modulate cardiorespiratory, feeding and gastric functions. • Vagal afferent (sensory) inputs are known to modulate brainstem synapses involved in visceral reflexes; however, the neurocircuits through which OXT exerts its actions are still unknown. • In this study we elucidate these mechanisms of actions and report that vagal sensory fibres control these neurocircuits in a conditionally controlled manner such that brainstem synapses can prepare the neurocircuits to allow appropriate modulation of digestive processes. • The results presented here improve our understanding of the central regulation of gastrointestinal functions and have the potential of being extended to the understanding of cardiorespiratory and feeding functions controlled by adjacent brainstem centres.Abstract Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT‐induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS–DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose‐dependent manner. The OXT‐induced gastric relaxation was enhanced following bethanechol and reduced by l ‐NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic‐mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric‐projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT‐induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit.