Structure, afferent innervation, and transmitter content of ganglia of the guinea pig gallbladder: Relationship to the enteric nervous system
Authors: Mawe Gary M. , Gershon Michael D. 
Published: January 2005

Although a well‐developed plexus of nerves and ganglia is known to be present in the wall of the gallbladder, little has previously been learned about the function or organization of this innervation. The current study was undertaken in order to evaluate the hypothesis that the ganglionated plexus of the gallbladder is analogous to elements of the enteric nervous system (ENS). The ganglionated plexus of the gallbladder was found to resemble closely the submucosal plexus of the small intestine in its organization into two irregular anastomosing and interwoven networks of ganglia, in the numbers of neurons per ganglion, and in the manifestation of histochemically demonstrable acetylcholinesterase activity in virtually all ganglion cells. In common with enteric ganglia, laminin immunoreactivity was observed to be excluded from the interiors of gallbladder ganglia, which were surrounded by a periganglionic laminin‐immunoreactive sheath. As in the submucosal plexus, intrinsic substance P‐, vasoactive intestinal polypeptide (VIP)‐, and neuropeptide Y (NPY)‐immunoreactive neurons were seen in the ganglionated plexus of the gallbladder. Extrinsic nerves in the gallbladder that degenerated following chemical sympathectomy with 6‐hydroxydopamine (6‐OHDA), and which contained NPY, tyrosine hydroxylase (TH), and dopamine‐β‐hydroxylase (DBH) immunoreactivities, formed a perivascular plexus closely associated with blood vessels. Endogenous catecholamines could also be demonstrated in these perivascular nerves by aldehyde‐induced histofluorescence. In addition to perivascular nerves, paravascular nerve bundles were observed that were loosely associated with vessels, did not degenerate following administration of 6‐OHDA, and contained NPY immunoreactivity. Other paravascular nerves, probably visceral sensory axons, coexpressed substance P and calcitonin‐generelated peptide (CGRP) immunoreactivities. The ganglionated plexus of the gallbladder resembled enteric ganglia in having intrinsic 5‐hydroxytryptamine (5‐HT)‐immunoreactive cells and highly varicose nerve fibers. The 5‐HT‐immunoreactive gallbladder axons were, like those of the gut, resistant to 6‐OHDA, and separate from fibers that expressed TH immunoreactivity. Differences between the ganglionated plexus of the gallbladder and enteric ganglia of the small intestine included in the gallbladder are (1) the presence of TH‐immunoreactive cells that contain an endogenous catecholamine, but not DBH; (2) DBH‐immunoreactive neurons, some of which coexpress substance P immunoreactivity, but which contain neither a catecholamine nor TH immunoreactivity; (3) an apparent absence of CGRP‐immunoreactive cell bodies. Retrograde tracers injected into the wall of the gallbladder revealed a direct innervation of the organ from neurons in ganglia of the myenteric plexus of the duodenum, in addition to neurons in the dorsal motor nuclei of the vagus, the celiac ganglion, and bilaterally in the nodose and T5‐T11 dorsal root ganglia. Because of its similar structure and receipt of a direct neural input from myenteric ganglia, the ganglionated plexus of the gallbladder should be regarded as an extension or division of the ENS; however, gallbladder‐specific specializations also occur. These specializations are similar to the regional differences found in enteric ganglia in different parts of the gut.