The terminal nerve and its relation with extrabulbar "olfactory" projections: lessons from lampreys and lungfishes

The definition of the terminal nerve has led to considerable confusion and controversy. This review analyzes the current state of knowledge as well as diverging opinions about the existence, components, and definition of terminal nerves or their components, with emphasis on lampreys and lungfishes. I will argue that the historical terminology regarding this cranial nerve embraces a definition of a terminal nerve that is compatible with its existence in all vertebrate species. This review further summarizes classical and more recent anatomical, developmental, neurochemical, and molecular evidence suggesting that a multitude of terminalis cell types, not only those expressing gonadotropin-releasing hormone, migrate various distances into the forebrain. This results in numerous morphological and neurochemically distinct phenotypes of neurons, with a continuum spanning from olfactory receptor-like neurons in the olfactory epithelium to typical large ganglion cells that accompany the classical olfactory projections. These cell bodies may lose their peripheral connections with the olfactory epithelium, and their central projections or cell bodies may enter the forebrain at several locations. Since "olfactory" marker proteins can be expressed in bona fide nervus terminalis cells, so-called extrabulbar "olfactory" projections may be a collection of disguised nervus terminalis components. If we do not allow this pleiomorphic collection of nerves to be considered within a terminal nerve framework, then the only alternative is to invent a highly species- and stage-specific, and, ultimately, thoroughly confusing nomenclature for neurons and nerve fibers that associate with the olfactory nerve and forebrain.     

Entropy of corneal nerve fibers distribution observed by laser scanning confocal microscopy: A noninvasive quantitative method to characterize the corneal innervation in Sjogren's syndrome patients

Sjogren's syndrome (SS) is a progressive autoimmune condition mainly affecting the salivary and lacrimal glands with an incidence of primary SS between 1/100 and 1/1,000. SS implies an alteration in the epithelium and subepithelium innervation, with consequent reduction of corneal sensitivity. It is necessary to have noninvasive quantitative methods to characterize the status of the corneal nerve fibers of the patients in order to choose and follow the best therapy. Entropy (information dimension) of the nerve corneal fibers distribution observed by confocal microscopy was evaluated in patients with primary SS (n = 30, 6 males, 24 females, 21–81 years), diagnosed by biopsy of salivary gland and blood tests and in sex‐ age‐matched healthy subjects (n = 12). Corneal nerve fiber density, Langerhans cell count, and cell density in the nerve plexus images were also evaluated. In selected patients salivary gland atrophy degree was also evaluated. Nerve corneal distribution observed by confocal microscopy is fractal. Entropy of the corneal nerve distribution statistically distinguishes between SS patients and healthy subjects: patients present a lower value of information dimension of the corneal nerve fibers distribution than healthy individuals (P < 0.001). Percentage of grouped cases classified by entropy according to the subjects (selected patients vs. healthy) showed a 100% sensitivity and 96% specificity, P < 0.0001 with a low value of coefficient of variation among the individuals (6–7 times lower than the other morphometric indexes). Entropy correlated with the severity of the disease (salivary gland atrophy degree, P < 0.01). Evaluation of entropy of the corneal nerve distribution observed by a laser confocal microscopy appears to quantitatively and noninvasively characterize an aspect of the SS patients in relation to the recognition of an impairment of their ocular surface, giving us for the first time a method to objectively and precisely characterize the corneal innervation status in the SS patients. Microsc. Res. Tech. 78:1069–1074, 2015. © 2015 Wiley Periodicals, Inc.     

Immunohistochemical and lectin histochemical studies on the developing olfactory organs of fetal camel

Little is known about the development of the olfactory organs of camel. In this study, prenatal development and neuronal differentiation of the vomeronasal organ (VNO) and the olfactory epithelium (OE) of the one‐humped camel were studied by immunohistochemistry and lectin histochemistry. A neuronal marker, protein gene product (PGP) 9.5, but not a marker of fully differentiated olfactory receptor cells, olfactory marker protein, intensely labeled the olfactory receptor cells of the VNO and OE at 395 mm, 510 mm, and 530 mm fetal ages, indicating that the olfactory receptor cells are differentiated, but not fully matured both in the VNO and the OE. In 187 mm and 190 mm fetuses, PGP 9.5 yielded faint immunoreactive signals in the VNO, but not in the OE, although the presence of olfactory receptor cells were demonstrated in both tissues by intense WGA and LEL stainings. We conclude that the camel VNO and OE bear differentiated, but still immature receptor cells; in addition, the onset of neuronal differentiation seems to be somewhat earlier in the VNO than in the OE till half of the prenatal life. Microsc. Res. Tech. 78:613–619, 2015. © 2015 Wiley Periodicals, Inc.     

Terminal nerve and vision

The vertebrate retina receives efferent input from different parts of the central nervous system. Efferent fibers are thought to influence retinal information processing but their functional role is not well understood. One of the best-described retinopetal fiber systems in teleost retinae belongs to the terminal nerve complex. Gonadotropin-releasing hormone (GnRH) and molluscan cardioexcitatory tetrapeptide (FMRFamide)-containing fibers from the ganglion of the terminal nerve form a dense fiber plexus in the retina at the border of the inner nuclear and inner plexiform layer. Peptide-containing fibers surround and contact perikarya of dopaminergic interplexiform cells in teleost retina. In vitro experiments demonstrated that exogenously supplied GnRH mediates dopaminergic effects on the membrane potential and on the morphology of dendritic tips (spinules) of cone horizontal cells. These effects can be specifically blocked by GnRH-antagonists, indicating that the release of dopamine and dopamine-dependent effects on light adaptation of retinal neurons are affected by the terminal nerve complex. Recent data have shown that olfactory information has an impact on retinal physiology, but its precise role is not clear. The efferent fiber of the terminal nerve complex is one of the first retinopetal fiber systems for which the sources of the fibers, their cellular targets, and several physiological, morphological, and behavioral effects are known. The terminal nerve complex is therefore a model system for the analysis of local information processing which is influenced by a distinct fiber projection.     

Fine structural aspects of secretion and extrinsic innervation in the olfactory mucosa.

The mucus at the surface of the olfactory mucosa constitutes the milieu in which perireceptor events associated with olfactory transduction occur. In this review, the ultrastructure of olfactory mucus and of the secretory cells that synthesize and secrete olfactory mucus in the vertebrate olfactory mucosa is described. Bowman's glands are present in the olfactory mucosa of all vertebrates except fish. They consist of acini, which may contain mucous or serous cells or both, and ducts that traverse the olfactory epithelium to deliver secretions to the epithelial surface. Sustentacular cells are present in the olfactory epithelium of all vertebrates. In fish, amphibia, reptiles, and birds, they are secretory; in mammals, they generally are considered to be "non-secretory," although they may participate in the regulation of the mucous composition through micropinocytotic secretion and uptake. Goblet cells occur in the olfactory epithelium of fish and secrete a mucous product. Secretion from Bowman's glands and vasomotor activity in the olfactory mucosa are regulated by neural elements extrinsic to the primary olfactory neurons. Nerve fibers described in early anatomical studies and characterized by immunohistochemical studies contain a variety of neuroactive peptides and have several targets within the olfactory mucosa. Ultrastructural studies of nerve terminals in the olfactory mucosa have demonstrated the presence of adrenergic, cholinergic and peptidergic input to glands, blood vessels, and melanocytes in the lamina propria and of peptidergic terminals in the olfactory epithelium. The neural origins of the extrinsic nerve fibers and terminals are the trigeminal, terminal, and autonomic systems.     

Trigeminal ganglion morphology in human fetus

The morphology of the trigeminal ganglion in human fetus was investigated by means of the tract‐tracing method using the lipophilic dye DiI‐C18‐(3) (1,1′‐double octadecane 3,3,3′3′‐tetramethyl indole carbonyl cyanine‐perchlorate), hematoxylin–eosin (HE) stain, and three‐dimensional computer reconstruction models. The trigeminal ganglion was flat in the dorsoventral direction, and DiI staining revealed that the trigeminal ganglion cells were somatotopically distributed in the ganglion in a way that reflected the mediolateral order of the three branches. Ganglion cells of the ophthalmic nerve were distributed in the anteromedial part of the trigeminal ganglion, those of the mandibular nerve were in the posterolateral part, and those of the maxillary nerve were localized in the intermediate part. DiI labeled both ganglion cells and nerve fibers in the trigeminal ganglion; the ganglion cells varied in size and appeared as round‐ or oval‐shaped, the neurites connected the cell soma, and some bipolar neurons were also observed. The number of embryonic trigeminal ganglion cells did not significantly change with gestational age, but the cell diameter, area, and perimeter significantly increased. The motor root leaves the pons, runs along the sensory root, passes the ventral surface of the ganglion, and finally runs together with the mandibular nerve. The findings reported here elucidate the morphology, development, and somatotopic organization of the trigeminal ganglion and reveal the trigeminal nerve motor root pathway along the trigeminal ganglion and mandibular nerve in the human fetus. Microsc. Res. Tech. 76:598–605, 2013. © 2013 Wiley Periodicals, Inc.     

Real‐time monitoring of the penetration of amphiphilic acrylate copolymer in leather using a fluorescent copolymer as tracer

A fluorescent tracer, poly (acrylic‐co‐stearyl acrylate‐co?3‐acryloyl fluorescein) [poly (AA‐co‐SA‐co‐Ac‐Flu)], used for real‐time monitoring the penetration of amphiphilic acrylate copolymer, poly (acrylic‐co‐stearyl acrylate) [poly (AA‐co‐SA)], in leather was synthesized by radical polymerization of acrylic, stearyl acrylate and fluorescent monomer, 3‐acryloyl fluorescein (Ac‐Flu). The structure, molecular weight, introduced fluorescent group content and fluorescent characteristics of the fluorescent tracer and target copolymer, amphiphilic acrylate copolymer, were also characterized. The results show that the tracer presents the similar structural characteristics to the target and enough fluorescence intensity with 1.68 wt % of the fluorescent monomer introduced amount. The vertical section of the leather treated with the target copolymer mixing with 7% of the tracer exhibits evident fluorescence, and the change of fluorescence intensity along with the vertical section with treating time increasing can reflect the penetration depth of the target copolymer. The introduction of the fluorescent group in polymer structure through copolymerization with a limited amount of fluorescent monomer, Ac‐Flu, is an effective way to make a tracer to monitor the penetration of the target in leather, which provides a new thought for the penetration research of syntans such as vinyl copolymer materials in leather manufacture. Microsc. Res. Tech. 78:1146–1153, 2015. © 2015 Wiley Periodicals, Inc.     

Distribution of CGRP in the minipig brainstem

For the first time, an in‐depth study has been made of the distribution of fibers and cell bodies containing calcitonin gene‐related peptide (CGRP) in the minipig brainstem using an indirect immunoperoxidase technique. The animals studied were not treated with colchicine. Cell bodies containing CGRP were found in 20 nuclei/regions of the brainstem. These perikarya were located in somatomotor, brachiomotor and raphae nuclei, nucleus ambiguus, substantia nigra, nucleus reticularis tegmenti pontis, nucleus prepositus hypoglossi, nuclei olivaris inferior and superior, nuclei pontis, formatio reticularis, nucleus dorsalis tegmenti of Gudden, and in the nucleus reticularis lateralis. Fourteen of the 20 brainstem nuclei showed a high density of immunoreactive cell bodies. In comparison with other species, the minipig, together with the rat, show the most widespread distribution of cell bodies containing CGRP in the mammalian brainstem. Immunoreactive fibers were also observed in the brainstem. However, in the minipig brainstem the density of these fibers is low, as in many brainstem nuclei only single immunoreactive fibers were observed. A high density of immunoreactive fibers was only observed in the pars caudalis of the nucleus tractus spinalis nervi trigemini and in the nucleus ventralis tegmenti of Gudden. According to the observed anatomical distribution of the immunoreactive structures containing CGRP, the peptide could be involved in motor, somatosensory, gustative, and autonomic mechanisms. Microsc. Res. Tech. 77:374–384, 2014. © 2014 Wiley Periodicals, Inc.     

The orexinergic system in rainbow trout Oncorhynchus mykiss and its regulation by dietary lipids

In this study, we report the distribution of orexin A (OXA), orexin B (OXB), and orexin receptor (OX2R) immunoreactive (ir) cells in the hypothalamus and gastrointestinal tract of Oncorhynchus mykiss fed diets with different dietary fatty acid compositions. Trout were fed five iso‐energetic experimental diets containing fish oil, or one of four different vegetable oils (olive, sunflower, linseed, and palm oils) as the added dietary lipid source for 12 weeks. OXA, OXB, and OX2R immunoreactive neurons and nervous fibers were identified in the lateral and ventro‐medial hypothalamus. OXA, OXB, and OX2R ir cells were found in the mucosa and glands of the stomach and in the mucosa of both the pyloric cecae and intestine. OX2R ir cells were localized in the mucosa layer of both the pyloric cecae and intestine. These immunohistochemical (IHC) results were confirmed via Western blotting. Antibodies against preproorexin (PPO) crossreacted with a band of ～16 kDa in the hypothalamus, stomach, pyloric cecae, and intestine. Antibodies against OX2R crossreacted with a band of ～38 kDa in the hypothalamus, pyloric cecae, and intestine. The presence and distribution of OXA, OXB, and OX2R ir cells in the hypothalamus and gastrointestinal tract did not appear to be affected by dietary oils. The presence of orexin system immunoreactive cells in the stomach, pyloric cecae, and intestine of rainbow trout, but not in the enteric nervous system, could suggest a possible role of these peptides as signaling of gastric emptying or endocrine modulation, implying a main local action played by orexins. Microsc. Res. Tech. 78:707–714, 2015. © 2015 Wiley Periodicals, Inc.     

Ultrastructural neurobiology of the olfactory mucosa of the brown trout, Salmo trutta.

This paper describes four investigations of the olfactory mucosa of the brown trout: 1) the ultrastructure of the olfactory mucosa as revealed by scanning (SEM), conventional transmission (TEM), and high voltage (HVEM) electron microscopy; 2) light and electron-microscopic investigations of retrograde transport of the tracer macromolecule horseradish peroxidase (HRP) when applied to the cut olfactory nerve; 3) SEM and TEM investigations of the effects of olfactory nerve transection on cell populations within the olfactory epithelium; and 4) ultrastructural investigations of reversible degeneration of olfactory receptors caused by elevated copper concentrations. The trout olfactory epithelium contains five cell types: ciliated epithelial cells, ciliated olfactory receptor cells, microvillar olfactory receptor cells, supporting cells, and basal cells. The ciliated and microvillar olfactory receptor cells and a small number of basal cells are backfilled by HRP when the tracer is applied to the cut olfactory nerve. When the olfactory nerve is cut, both ciliated and microvillar olfactory receptor cells degenerate within 2 days and are morphologically intact again within 8 days. When wild trout are taken from their native stream and placed in tanks with elevated copper concentrations, ciliated and microvillar cells degenerate. Replacement of these trout into their stream of origin is followed by morphologic restoration of both types of olfactory receptor cells. Ciliated and microvillar receptor cells are primary sensory bipolar neurons whose dendrites make contact with the environment; their axons travel directly to the brain. Consequently, substances can be transported directly from the environment into the brain via these "naked neurons." Since fish cannot escape from the water in which they swim, and since that water may occasionally contain brain-toxic substances, the ability to close off--and later reopen--this anatomic gateway to the brain would confer a tremendous selective advantage upon animals that evolved the "brain-sparing" capacity to do so. Consequently, the unique regenerative powers of vertebrate olfactory receptor neurons may have their evolutionary origin in fishes.     

The nasal cavity of the sheep and its olfactory sensory epithelium

Macro and microdissection methods, conventional histology and immunohistochemical procedures were used to investigate the nasal cavity and turbinate complex in fetal and adult sheep, with special attention to the ethmoturbinates, the vestibular mucosa, and the septal mucosa posterior to the vomeronasal organ. The ectoturbinates, which are variable in number and size, emerge and develop later than the endoturbinates. The olfactory sensory epithelium is composed of basal cells, neurons, and sustentacular cells organized in strata, but numerous different types are distinguishable on the basis of their thickness and other properties; all variants are present on the more developed turbinates, endoturbinates II and III. Mature neurons and olfactory nerve bundles express olfactory marker protein. We found no structure with the characteristics that in mouse define the septal organ or the ganglion of Grüneberg. Our results thus suggest that in sheep olfactory sensory neurons are exclusively concentrated in the main olfactory epithelium and (to a lesser extent) in the vomeronasal organ. Microsc. Res. Tech. 77:1052–1059, 2014. © 2014 Wiley Periodicals, Inc.     

Peptides in frog brain areas processing visual information

Vision is the most important sensory modality to anurans and a great deal of work in terms of hodological, physiological, and behavioral studies has been devoted to the visual system. The aim of this account is to survey data about the distribution of peptides in primary (lateral geniculate complex, pretectum, tectum) and secondary (striatum, anterodorsal and anteroventral tegmental nuclei, isthmic nucleus) visual relay centers. The emphasis is on general traits but interspecies variations are also noted. The smallest amount of peptide-containing neuronal elements was found in the lateral geniculate complex, where primarily nerve fibers showed immunostaining. All peptides found in the lateral geniculate complex, except two, occurred in the pretectum together with four other peptides. A large number of neurons showing intense neuropeptide thyrosine-like immunoreactivity was characteristic here. The mesencephalic tectum was the richest in peptide-like immunoreactive neuronal elements. Almost all peptides investigated were present mainly in fibers, but 9 peptides were found also in cells. The immunoreactive fibers show a complicated overlapping laminar arrangement. Cholecystokinin octapeptide, enkephalins, neuropeptide tyrosine, and substance P (not discussed here) gave the most prominent immunoreactivity. Several peptides also occur in the tectum of fishes, reptiles, birds, and mammals. Peptides in various combinations were found in the striatum, the anterodorsal- and anteroventral tegmental nucleus, and the isthmic nucleus that receive projections from the primary visual centers. The functional significance of peptides in visual information processing is not known. The only exception is neuropeptide tyrosine, which was found to be inhibitory on retinotectal synapses.     

Effects of chemical agents on physical properties and structure of primary pulp chamber dentin

This study evaluated the effects of chemical agents on the physical properties and structure of primary pulp chamber dentin using surface roughness, microhardness tests, and scanning electron microscopy (SEM). Twenty‐five primary teeth were sectioned exposing the pulp chamber and were divided into five groups (n = 5): NT, no treatment; SH1, 1% sodium hypochlorite (NaOCl); SH1U, 1% NaOCl + Endo‐PTC^®; SH1E, 1% NaOCl + 17% EDTA; and E, 17% EDTA. After dentin treatment, the specimens were submitted to roughness, microhardness testing, and SEM analysis. Roughness and microhardness data were submitted to one‐way ANOVA and Tukey's test (P < 0.05). The SH1E group showed the highest roughness, followed by the E group (P < 0.05) when compared with the NT, SH1, and SH1U groups. Microhardness values of SH1 and SH1U showed no significant difference as compared to the NT (control) group (P > 0.05). Microhardness values could not be obtained in the EDTA groups (SH1E and E). The presence of intertubular dentin with opened dentin tubules was observed in the NT, SH1, and SH1U groups. SH1E showed eroded and disorganized dentin with few opened tubules and the intertubular/peritubular dentin was partially removed. Considering the physical and structural approaches and the chemical agents studied, it can be concluded that NaOCl and NaOCl associated with Endo‐PTC^® were the agents that promoted the smallest changes in surface roughness, microhardness, and structure of the pulp chamber dentin of primary teeth. Microsc. Res. Tech. 77:52–56, 2014. © 2013 Wiley Periodicals, Inc.     

The olfactory organ of the trout Salmo trutta fario: A novel localization for a progestin receptor

A progestin receptor (PR) has been detected in the olfactory organ of the trout Salmo trutta fario. The specificity of this receptor was high for 17α,20β‐dihydroxy‐4‐pregnen‐3‐one (17α,20β‐DP), but it also bound 17α‐hydroxy‐progesterone (17α‐OHP) and 21‐hydroxyprogesterone (21‐OHP), even when present at low concentrations (10‐fold in relative binding affinity assay). Progesterone (P) competed effectively at much higher concentrations (1,000‐fold in relative binding affinity assay). Immunohistochemical studies carried out with three different monoclonal antibodies against human progesterone receptor (hPR), chicken progesterone receptor hinge region (cPR), and chicken progesterone receptor A/B domain (PR22), revealed that immunoreactivity was present in the epithelium of the olfactory organ of females and males of the trout Salmo trutta fario only against hPR. Western blotting showed two hPR immunoreactive bands of about 62 and 66 kDa. Finally, a portion of the cDNA of about 300 nucleotides extending over the DNA binding domain and the ligand binding domain was cloned and sequenced, revealing a high degree of sequence homology of the PR in Salmo trutta fario with the PR in other teleosts. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.     

Distribution of ghrelin peptide in the gastrointestinal tract of stomachless and stomach-containing teleosts

The occurrence and localization of ghrelin peptide in the gastrointestinal tract of Carassius auratus and Dicentrarchus labrax, two fish species that exhibit different feeding behavior, different habitats, and different anatomical organizations of the gastroenteric tract, were examined by immunohistochemical methods and western blotting analysis. All of the gastrointestinal segments studied displayed immunohistochemical localizations of ghrelin peptide. Numerous single or clustered immunoreactive cells were found along the gastric folds, particularly in the pyloric region of Dicentrarcus labrax, whereas scattered ghrelin immunoreactive cells were observed in the intestinal epithelium of both fish species. Double immunolabeling PGP 9.5/ghrelin demonstrated the localization of ghrelin peptide also in nerve fibers and neuronal cells of the submucosal and myenteric plexuses, often in association with vascular structures. Western blotting analysis confirmed the presence of ghrelin peptide in the gatrointestinal tract of both species studied, whose molecular weight was similar to that of the corresponding mammalian prepro-ghrelin. The findings could support the hypothesis that this peptide is an important appetite regulator in fish and could confirm the presence of the ghrelin peptide, starting from its precursor proteins, in the gastrointestinal tract of the goldfish and the sea bass. Microsc. Res. Tech. 2009. © 2009 Wiley-Liss, Inc.     

Mapping of somatostatin‐28 (1‐12) in the alpaca (Lama pacos) brainstem

Using an indirect immunoperoxidase technique, we studied the distribution of cell bodies and fibers containing somatostatin‐28 (1‐12) in the alpaca brainstem. Immunoreactive fibers were widely distributed throughout the whole brainstem: 34 brainstem nuclei/regions showed a high or a moderate density of these fibers. Perikarya containing the peptide were widely distributed throughout the mesencephalon, pons and medulla oblongata. Cell bodies containing somatostatin‐28 (1‐12) were observed in the lateral and medial divisions of the marginal nucleus of the brachium conjunctivum, reticular formation (mesencephalon, pons and medulla oblongata), inferior colliculus, periaqueductal gray, superior colliculus, pericentral division of the dorsal tegmental nucleus, interpeduncular nucleus, nucleus of the trapezoid body, vestibular nucleus, motor dorsal nucleus of the vagus, nucleus of the solitary tract, nucleus praepositus hypoglossi, and in the substantia nigra. This widespread distribution indicates that somatostatin‐28 (1‐12) is involved in multiple physiological actions in the alpaca brainstem. Microsc. Res. Tech. 78:363–374, 2015. © 2015 Wiley Periodicals, Inc.     

Carotid body and glomus cells distributed in the wall of the common carotid artery in the bird

In the bird the carotid body is located between the distal (nodose) ganglion of the vagus nerve and the recurrent laryngeal nerve at the beginning of the common carotid artery, that is, the organ is located at the cervicothoracic border. The chicken carotid body receives numerous branches from the vagus and the recurrent laryngeal nerves. In addition, dense networks of the peptidergic nerve fibers immunoreactive for substance P, calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), galanin, and neuropeptide Y (NPY) are distributed in and around the carotid body parenchyma. The substance P- and CGRP-immunoreactive fibers are derived from both the superior and inferior ganglia of the vagus nerve. The VIP-, galanin-, and NPY-immunoreactive fibers originate from the 14th cervical ganglion of the sympathetic trunk. The endocrine organs including the thyroid gland, parathyroid glands, carotid body, and ultimobranchial gland are situated as a continuous series along the common carotid artery. The organs are supplied with arteries arising as one trunk from the common carotid artery. Glomus cells are widely distributed not only in the carotid body but also in the wall of the common carotid artery and around the common trunk and its branches. The glomus cells of the chicken carotid body exhibit intense immunoreactivity for serotonin, tyrosine hydroxylase, and chromogranin A. The cells located in the wall of the common carotid artery further express NPY mRNA and peptide. In the chickens exposed to isocapnic hypoxia for 35 days, 3-4-fold increase of the carotid body volume is induced and the carotid body glomus cells show enhanced synthetic and secretory activities. On the other hand, the cells in the wall of the common carotid artery display little changes after the long-term hypoxia, having different functions from the carotid body. The carotid body rudiment is formed in the lateral wall of the third branchial artery. The neural cells immunoreactive for TuJ1, PGP 9.5, and HNK-1, which are continuous with the inferior vagal (nodose) ganglion, first surround and then invade both the carotid body rudiment and the other portions of the third branchial artery, becoming glomus cells.