Characterization of noradrenergic transmission at the dorsal motor nucleus of the vagus involved in reflex control of fundus tone

Abstract

Quantitative analysis of innervation to dorsal motor nucleus of the vagus (DMV) fundus-projecting neurons indicates that approximately 17% of input neurons are noradrenergic. To determine whether this small percentage of neurons innervating DMV output to the stomach is physiologically relevant, we evaluated the role of norepinephrine at the DMV in mediating a vagovagal reflex controlling the fundus. A strain gauge was sutured onto the fundus of isoflurane-anesthetized rats to monitor changes in tone evoked by esophageal distension (ED). ED produced a decrease in fundus tone of 0.31 +/- 0.02 g (P < 0.05), which could be reproduced after a 30-min interval between distensions. Bilateral cervical vagotomy and/or pretreatment with intravenous atropine methylbromide prevented the reflex-induced fundus relaxation. In contrast, intravenous N(G)-nitro-L-arginine methyl ester had no effect. Bilateral microinjection of alpha2-adrenoreceptor antagonists (yohimbine and RS-79948) into the DMV also prevented the response. Before microinjection of alpha2-adrenoreceptor antagonists, ED decreased fundus tone by 0.33 +/- 0.05 g (P < 0.05). After antagonist microinjection, ED decreased fundus tone by only 0.05 +/- 0.06 g (P > 0.05). Bilateral microinjection of prazosin into the DMV had no effect on the response. Microinjection of norepinephrine into the DMV mimicked the effect of ED and was also prevented by prior microinjection of an alpha2-adrenoreceptor antagonist. Our results indicate that noradrenergic innervation of DMV fundus-projecting neurons is physiologically important and suggest that norepinephrine released at the DMV acts on alpha2-adrenoreceptors to inhibit activity in a cholinergic-cholinergic excitatory pathway to the fundus.

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

“…With regard to the view that two parallel pathways from the DMV participate in resting gastric motility, our data are not supportive of this position. Consistent with our previous reports (8,10,11,18,32), the present studies provide further evidence that in two additional conditions, namely baseline conditions and GABA A receptor blockade in the medial subnucleus of the tractus solitarius (mNTS), inhibition of gastric motility produced under these conditions is not due to activation of NANC postganglionic neurons. …”

“…In turn, neurons in the NTS project to the DMV, and this latter nucleus contains the preganglionic parasympathetic neurons that innervate the stomach (20). Evidence that the above neurons and hindbrain nuclei in the rat represent the vagovagal reflex circuitry is as follows: 1) activation of the vagal sensory neurons by distending the upper GI tract excites NTS neurons and inhibits DMV neurons (23,41); 2) activation of vagal sensory neurons by distending the upper GI tract results in an inhibition of gastric motility that is blocked by either bilateral microinjection of tetrodotoxin into the mNTS (10), bilateral cervical vagotomy (10,18), or intravenous administration of a quaternary form of atropine (18); 3) activation of NTS neurons with microinjection of L-glutamate at the site where vagal afferent nerves terminate results in inhibition of gastric motility that is blocked by bilateral cervical vagotomy (10); and 4) activation of DMV neurons with microinjection of L-glutamate increases gastric motility that is blocked by either cervical vagotomy (8,10) or intravenous administration of a quaternary form of atropine (8).…”

“…Microinjection of BMI was then repeated after IGP and arterial blood pressure had stabilized from the intravenously administered drug (ϳ7-10 min). The doses of atropine methylbromide and L-NAME were based on our previous studies (8,18).…”

“…There is considerable evidence that GABAergic neurons are responsible for a significant part of this communication (9, 35). There is also evidence that noradrenergic neurons take part in this communication process (10,11,18,26,29). Both the GABAergic and noradrenergic neurons are considered to be NTS projection neurons that synapse onto DMV gastric-projecting neurons (9,10,29).…”

“…The first view persists despite both anatomical and functional in vitro evidence of local inhibitory processing within the NTS (13,15,17,21). The second view lacks functional evidence for the NANC pathway as it relates to gastric motility (8,18). Nevertheless, these two views continue to dominate this field of research (5,19,28,36,41,42).…”