Vagal Intramuscular Arrays: The Specialized Mechanoreceptor Arbors That Innervate the Smooth Muscle Layers of the Stomach Examined in the Rat

Abstract

The fundamental roles that the stomach plays in ingestion and digestion notwithstanding, little morphological information is available on vagal intramuscular arrays (IMAs), the afferents that innervate gastric smooth muscle. To characterize IMAs better, rats were given injections of dextran biotin in the nodose ganglia, and, after tracer transport, stomach whole mounts were collected. Specimens were processed for avidin-biotin permanent labeling, and subsets of the whole mounts were immunohistochemically processed for c-Kit or stained with cuprolinic blue. IMAs (n = 184) were digitized for morphometry and mapping. Throughout the gastric muscle wall, IMAs possessed common phenotypic features. Each IMA was generated by a parent neurite arborizing extensively, forming an array of multiple (mean = 212) branches averaging 193 μm in length. These branches paralleled, and coursed in apposition with, bundles of muscle fibers and interstitial cells of Cajal. Individual arrays averaged 4.3 mm in length and innervated volumes of muscle sheet, presumptive receptive fields, averaging 0.1 mm 3 . Evaluated by region and by muscle sheet, IMAs displayed architectural adaptations to the different loci. A subset (32%) of circular muscle IMAs issued specialized polymorphic collaterals to myenteric ganglia, and a subset (41%) of antral longitudinal muscle IMAs formed specialized net endings associated with the serosal boundary. IMAs were concentrated in regional patterns that correlated with the unique biomechanical adaptations of the stomach, specifically proximal stomach reservoir functions and antral emptying operations. Overall, the structural adaptations and distributions of the IMAs were consonant with the hypothesized stretch receptor roles of the afferents. INDEXING TERMSantrum; corpus; forestomach; nodose; vagus; visceral afferent; RRID:AB_354750; RRID:nif-0000-10294 HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe extrinsic innervation of the stomach has not been fully characterized. In spite of the critical roles that the stomach plays in controlling both ingestion and digestion, the vagal sensory projections to the gastric wall are among the elements that have been less thoroughly described. The lack of such basic information is paradoxical in view of the fact that major gastrointestinal (GI) disorders such as gastroparesis, gastroesophageal reflux disease, and obesity are currently treated with gastric interventions predicated only on incomplete descriptions of stomach innervation. To address, in part, the relative lack of information available for the extrinsic sensory projections to the stomach, specifically the dearth of details on the recently discovered vagal afferent endings called intramuscular arrays (IMAs), the present experiment inventories and characterizes more fully these afferents that innervate smooth muscle fibers in the gastric wall.Traditionally, the vagus, the nerve supplying the bulk of the nonnociceptive extrinsic innervation of the stomach (Iggo,...

Distribution and morphology of P2X3‐immunoreactive subserosal afferent nerve endings in the rat gastric antrum

“…Since antral peristalsis is responsible for the trituration, mixing, and emptying of gastric contents, P2X3‐immunoreactive subserosal nerve endings may be activated under these digestive processes. The total number of IGLEs and the volume of muscle sheets innervated by IMAs in the gastric antrum were smaller than those of the fundus and corpus, as shown by anterograde tracing into the rat NG (Berthoud et al, 1997; Powley et al, 2016). These findings suggest that large net‐like structures of P2X3‐immunoreactive subserosal nerve endings compensate for the mechanoreceptive field during antral peristalsis.…”

“…Furthermore, two‐dimensionally extended net‐like terminal structures formed by multiple parent axons of P2X3‐immunoreactive nerve endings have been shown to resemble mechanosensory endings such as the laminar endings in the laryngeal mucosa (Soda & Yamamoto, 2012), and sensory endings in airway smooth muscle (Brouns et al, 2006) and visceral pleura (Pintelon et al, 2007). Since antral web endings were formed by a subset (41%) of vagal afferents forming IMAs in the LM layers, as shown by anterograde tracing into the rat NG (Powley et al, 2012; Powley et al, 2016), P2X3‐immunoreactive subserosal nerve endings may be a subtype of vagal mechanoreceptors in the distal antrum of the lesser curvature. Video spatiotemporal mapping techniques using ex vivo preparations of the rat stomach have revealed that intraluminal infusion of saline‐induced‐antral peristalsis dynamically changes the area strain rate of the distal antrum in the lesser curvature (Lentle et al, 2016).…”

“…IGLEs arborized laminar terminal branches covering myenteric ganglion neurons between smooth muscle layers, and were electrophysiologically characterized as tension-sensitive mechanoreceptors with highly focal receptive fields (Zagorodnyuk et al, 2001), whereas IMAs formed rectilinear terminal branches that run parallel to smooth muscle fibers and therefore are suggested to be stretch (or length) mechanoreceptors (Phillips & Powley, 2000;Powley et al, 2008;Powley & Phillips, 2011). Furthermore, anterograde tracing studies revealed vagal afferents composing IMAs within the longitudinal muscle (LM) layer to form the honeycombed network structures of lamellar neurites, called "antral web endings," in subserosal tissue (SS) of the rat antral lesser curvature (Powley et al, 2012(Powley et al, , 2013Powley et al, 2016).…”

Gastric Neurons in the Nucleus Tractus Solitarius are Selective to the Orientation of Gastric Electrical Stimulation

“…Target 2 (Powley et al, 2016;Tan et al, 2021). B and E show the pairing of the anode (red) and the cathode (black) for delivering a current pulse in one of four different directions (0 o , 270 o , 180 o , and 90 o ).…”

“…It has two subtypes, namely longitudinal and circular IMAs, which target longitudinal and circular muscles, respectively. Both subtypes show regional distributions overlapping in the antrum but distinctive in the forestomach (or fundus) (Powley et al, 2016;Tan et al, 2021).…”