Small Ganglion Research Articles

A minimal model of C. elegans forward locomotion: the larval L1 circuit

The nematode Caernohabditis elegans possesses one of the simplest central nervous systems, and by far the best characterized. In the adult, the nervous system consists of a mere 302 neurons, of which the majority are located in the head, and the rest are distributed in the pharynx, along the ventral cord or in small ganglia. In particular, the local control (along the body) of the worm’s sinuous undulations is instantiated by 8 classes of ventral cord motor neurons. But of those, only 3 classes exist as the larva hatches out of the egg (the so called L1 stage in development). This appears quite remarkable, given the similar repertoire of behaviors in the larva, as compared to the fully developed adult. Here, we ask what minimal design principles must apply for the L1 circuit to generate robust forward locomotion. Robustness is taken to mean effective locomotion in different physical environments (e.g. high viscosity agar gels versus water) [1,2]. To address this challenge, we adopt an integrated neuromechanical model of forward locomotion in the adult that consists of the ventral cord nervous system, muscles, a body and a physical environment [2], and adapt the model nervous system and muscles to match the L1. In particular, we assume the forward locomotion control in the L1 consists of repeating units, each consisting only of a pair of neurons: one excitatory DB and one inhibitory DD. DB neurons are modeled as bistable elements [2] innervating dorsal muscles, and DD neurons are modeled as linear elements inhibiting ventral muscles. High level control is modeled with an on/off AVB unit that drive all B-neurons. The rhythm is generated entirely on the dorsal side and is achieved by a closed-loop proprioceptive feedback (via postulated stretch sensitivity of DB neurons). Inhibitory neurons receive synaptic inputs from the local DB neuron and are therefore enslaved to its oscillations. The integrated model successfully generates and propagates coordinated undulations on agar and liquid model environments. In the model, both of these behaviors are achieved by a single (i.e., fixedparameter) model worm. The model makes a number of relatively easily testable predictions: 1) L1 larva have a minimal, reflex-driven mechanism to control body undulations. 2) Inhibitory D-neurons are essential for forward locomotion in the L1. 3) Muscle properties must differ substantially between the ventral and dorsal side (specifically, ventral but not dorsal muscles must be spontaneously active).

39. The prevalence of intestinal neuronal dysplasia hirschsprung’s disease patients in Malaysia

Background Hirschsprung’s disease (HD) is due to malfunction of neural crest cell migration to the distal bowel, resulting in colonic aganglionosis. Hypoganglionosis and intestinal neuronal dysplasia (IND) are other neuronal causes of paediatric intestinal obstruction. These two entities have been reported to occur concurrently with HD. Their occurrence in the Malaysian HD population remains unknown. This knowledge is important to avoid the diagnostic pitfalls of transition zone evaluation, especially in intraoperative frozen section procedure. Aim To investigate the prevalence of hypoganglionosis and IND in resected bowel specimens for HD. Methods Thirty-nine resected bowel specimens from HD cases were retrieved from the archives of Pathology Department, Hospital Kuala Lumpur. The H&E stained sections from these cases were reviewed for the neuronal abnormalities stated above. Results Demographically, 79.4% of the patients were male. The age at operation ranged from 11 weeks to 4.9 years. Culturally, 66% were Malays, 17% Chinese, 12.8% indigenous Borneo ethnic group and 2.5% Indian. All of the cases had recto-sigmoid disease. Giant ganglia and hypoganglionosis were seen in 7 (17%) and 4 (10.3%) cases, respectively. In addition, an excess of small ganglions were present within the transtition zone of 24 cases (61.5%), while ectopic ganglia were observed in 2 cases. Conclusion IND is not uncommon in HD patients in Malaysia. This is important to appreciate, especially in the assessment of resection margins of HD.

Expression of peripherin in human cochlea

The organ of Corti contains two different types of auditory receptors; the inner (IHCs) and outer (OHCs) hair cells. This dualism is further represented in their innervation, IHCs being innervated by type I neurons, and OHCs by type II neurons (in man, named small ganglion cells). Two efferent systems are also present. Here, we have analyzed the expression of the 57-kDa neuron-specific intermediate filament protein peripherin (PP) in human cochlea. In the human organ of Corti, PP seems to be specifically expressed in OHC afferents. Small or type II spiral ganglion cell bodies also intensely express PP. Thus, PP can be used as a marker for the characterization of the innervation of the OHC system in man.

Nerve cell bodies and small ganglia in the connective tissue stroma of human submandibular glands

The objective of the study was to investigate the presence and distribution of nerve cell bodies and small ganglia in the stroma of human submandibular gland. A retrospective immunohistochemical study in 13 human submandibular glands, fixed in neutral buffered formalin and embedded in paraffin wax, was undertaken. Six glands were excised in the course of radical neck dissection for oral squamous cell carcinoma and were disease-free, six showed sialadenitis, and one was involved by tuberculosis. Primary antibodies applied were neuron specific enolase, synaptophysin, and glial fibrilliary acidic protein. Neuron specific enolase and synaptophysin positive nerve cell bodies and small ganglia were found in 8/13 and 13/13 glands, respectively. They were found in the interlobular connective tissue stroma of human SMG, in close association to salivary parenchymal cells and blood vessels, and some of them were incorporated in GFAP positive peripheral nerves. To our knowledge, nerve cell bodies and small ganglia have been described only in the connective tissue stroma of autotransplanted human SMG and their functional importance is not clear.

Pneumoperitoneum without intestinal perforation in an adolescent girl

Pneumoperitoneum without intestinal perforation in an adolescent girl

Temporal lobe herniation of developmental origin: a novel radiological association with open spina bifida and Chiari II malformation

Dear Editor,With regards to our recent paper on the phenomenon ofchronic uncal herniation [1], we came across an 11-year-oldchild with open spina bifida, associated with a temporallobe herniation, albeit with a difference.TheboywedescribewasbornwithanopenspinabifidaofL4level.Hehadahistoryoflumbarmyelomeningocelerepairat day1 of life. He had a ventriculoperitoneal shunt forprogressive hydrocephalus at 2 weeks of age. Subsequently,he had foramen magnum decompression when he was2 months old for persistent symptoms of brainstem compres-sionincludingrecurrentapneas.Presentlythechildhasseverepsychomotor retardation and is spastic quadriparetic.A recent follow-up MRI of the brain showed herniationof the temporal lobe and downwardly displaced occipitallobes associated with a thinned out vermis, an almostnonexistent cerebellum, thinning of the brainstem, and adeficient tentorium cerebelli (Fig. 1). His older imagingfrom his infancy demonstrated the same phenomenon oftemporal lobe herniation in association with the otheranomalies usually associated with Chiari II malformation[2, 3]. The finding of cerebral herniation in Chiari IImalformation to the best of our knowledge has previouslynot been described.In our previous paper on the similar phenomenon, wehad proposed that chronic uncal herniation was a conse-quence of the presence of a cystoperitoneal shunt and thenegative pressure gradient it created across the tentorium,and it was a treatment sequel of posterior fossa cysticcollection shunting [1]. We propose that the cerebral uncalherniation in this described child with Chiari II malforma-tion may be a sequel of the open spinal defect-associatedpressure gradient between the supratentorial compartmentand infratentorial compartment, existing prior to the closureof the CSF leak at the spinal level, analogous to thetonsillar herniation (as explained by the unified hypothesisby McLone and Knepper [4]) occurring in open spinaldefects and hence is a developmental intrauterine anomaly.The cerebral herniation probably represented an extremityof the spectrum. Note the severely hypoplastic cerebellum(“ vanishing” cerebellum [4]) in the figure (Fig. 1). It ispossible a relatively “spacious” posterior fossa instead ofthe usual tight posterior fossa, due to lack of cerebellum incombination with a widened tentorial hiatus and partlydeficient tentorium contributed to the picture in this specificchild and situation (Fig. 1). Also, the perinatal hydroceph-alus may have been contributory to the picture.Chiari II malformation is characterized by mesodermaldysplasia and premature condensation of the basilar skullanlagen, small and dysplastic lower cranial nerve ganglia,deficient tentorium cerebelli, hypoplastic and dysmorphiccerebellum, and thickened basal meninges. These anomaliesall are attributable to defective or deficient mesenchyme,which presumably deprived the skull base, hindbrain, andrhombencephalon of normal inductive effects [5].Our patient had no significant progression of neurolog-ical status; hence, probably the finding of temporal lobe

Changes in bladder innervation in a mouse model of Alzheimer's disease

Aim The aims of this study were to compare the structure of bladders from a transgenic mouse model of Alzheimer's disease with age matched control animals and to explore the idea that any structural differences might be related to functional bladder changes associated with the condition. Materials and methods Two groups of mice were used. Transgenic animals in which the murine Amyloid Precursor Protein (APP) gene has been partly replaced by the human APP including both the Swedish and London mutations and that overexpress a mutant of the human Presenilin 1 gene (PS1M146L) driven by the PDGF promoter. The transgenic mice (App SL/PS1 M146L) aged 24 ± 3 months were used. The second group was an age matched control group of C57 black mice. The bladders from each group were isolated, fixed in 4% paraformaldehyde and prepared for immunohistochemistry. Antibodies to the vesicular acetylcholine transporter (VAChT) and neuronal nitric oxide synthase (nNOS) were used to identify neural structures. Results Cholinergic nerves (VAChT +) were observed in the inner and outer muscle bundles of App SL/PS1 M146L and control mice. No major differences were noted in the distribution of these fibres. In contrast, there was a distinct difference in the innervation of the sub-urothelial layer. In App1 SL/PS1 M146L mice there were numerous VAChT and nNOS positive fibres in sharp contrast to the paucity of similar nerves in control animals. VAChT and nNOS did not appear to co-localise in the same nerve fibres within the lamina propria. Pairs of nerve fibres, nNOS + and VAChT +, were observed to be intertwined and run in close proximity. A particularly unusual feature of the App SL/PS1 M146L mouse bladder was the presence of neurones within the bladder wall. These nerve cell bodies were seen in all App SL/PS1 M146L mouse bladders. The neurones could be found singly or in small ganglion like groups of cells and were located in all layers of the bladder wall (sub-urothelium, in the lamina propria adjacent to the inner muscle and within the inner muscle and outer muscle layers). No nerve cells or small ganglia were noted in any of the control bladders studied. Conclusions There are structural differences in the bladders of App SL/PS1 M146L mice compared to control animals. These differences are associated with sub-urothelial nerves which, because of their location, are likely to be sensory fibres. This may lead to a changed sensory processing from the App SL/PS1 M146L bladders. The physiological role of the intra-mural neurones and ganglia is not known. It is speculated that they may be associated with peripheral motor/sensory mechanisms linked to the generation and modulation of sensation.

Excitatory conductances drive S-ON and LM-OFF opponency in small bistratified blue-ON ganglion cells

Excitatory conductances drive S-ON and LM-OFF opponency in small bistratified blue-ON ganglion cells

Tracheal innervation is abnormal in rats with experimental congenital diaphragmatic hernia

Background Tracheobronchial motility influences lung development. Lung hypoplasia and lung sequelae accompany congenital diaphragmatic hernia (CDH) in which the vagus nerves and esophageal innervation are abnormal. As the vagus supplies tracheal innervation, this study tested the hypothesis that it might also be abnormal in rats with CDH. Material and Methods Intrinsic ganglia were counted and measured in whole mount acetylcholinesterase-stained tracheas from CDH and control E21 fetal rats. The relative surfaces occupied by neural structures were measured in tracheal sections immunostained for p75 NTR and PGP 9.5. PGP 9.5 protein and mRNA expression were determined. Mann-Whitney tests were used for comparisons between groups using P < .05 as significant. Results p75 NTR staining showed the neural crest origin of tracheal innervation. Scarce neural structures and smaller ganglia were found in CDH fetuses. PGP 9.5 protein expression was decreased in CDH fetuses, whereas PGP 9.5 mRNA levels were increased in comparison with controls. Conclusions Decreased density of neural structures and size of intramural ganglia, reduced expression of neural tissue and PGP 9.5 protein, and increased levels of PGP 9.5 mRNA reveal deficient tracheal innervation in rats with CDH. If similar anomalies exist in the human condition, they could contribute to explaining the pathogenesis of lung hypoplasia and bronchopulmonary sequelae.

Spinal nerve ligation causes a selective upregulation of alpha2delta immunoreactivity on small diameter dorsal root ganglion neurons

Spinal nerve ligation causes a selective upregulation of alpha2delta immunoreactivity on small diameter dorsal root ganglion neurons

Melanocytic medulloblastoma with ganglioneurocytomatous differentiation: A case report

Melanotic or melanocytic medulloblastoma is a rare variant of medulloblastoma, especially when the tumor shows advanced neuronal differentiation. We report a case of this tumor, which developed in the cerebellar vermis in an 8-year-old girl. Initial biopsy specimens were identified as classical medulloblastoma with a high MIB1 index. Surgical removal of the tumor was performed after chemo-radiotherapy, and black pigments were noticed on the tumor surface. Histologically, the tumor was composed of classical medulloblastoma with the presence of pigmented epithelial cells forming tubules and clusters. Immunohistochemically, the pigmented tumor cells were positive for S100 protein, HMB45, and MART1, indicating that the pigments were derived from melanosomes, and these features were compatible with melanocytic medulloblastoma. Interestingly, some of the non-pigmented or amelanotic tumor cells were also positive for HMB45 and S100 protein. Although the tumor showed an unusual cell combination, it was distinguished from atypical teratoid/rhabdoid tumor (AT/RT) by nuclear expression of INI1/BAF45 protein. The tumor also possessed ganglion-like cells within the neuropil matrix, which resembled small mature ganglion cells, and was consequently designated as ganglioneurocytoma. The melanotic medulloblastoma and part of the ganglioneurocytomatous area were fused with each other. Hence, the present case provides new information indicating that melanocytic medulloblastoma differs from AT/RT, and that it can exhibit advanced neuronal differentiation. In addition, reduction of the tumor MIB1 index was observed after chemo-radiotherapy.

Autonomic Innervation of Pancreas in Egyptian Spiny Mouse (Acomys cahirinus, Desmarest)

The aim of the study was to obtain details of the morphology of the autonomic innervation of pancreas. Six adult Egyptian spiny mice (Acomys cahirinus, Desmarest) were studied for the presence and location of autonomic fibres and cells in the pancreas. The macromorphological investigations were performed using the thiocholine method adapted for this type of specimens. For processing tissues two histochemical techniques were used: thiocholine method on activity of AChE and the glyoxylic acid method for adrenergic structures. Cholinergic fibres and small autonomic ganglia were found among the secretory sections and along the pancreatic duct and both pancreaticoduodenal arteries, and its branches, reaching the Langerhans islets and forming around them a kind of net. From 24 to 40 AChE-positive ganglions in the whole exocrine part were observed. The highest density of cholinergic fibres was observed in the head of pancreas. Numerous adrenergic fibres that accompanied blood vessels as well as interlobular and intralobular ducts were found inside the exocrine parts of the pancreas. Neither adrenergic cells or adrenergic fibres were observed inside the pancreatic islets. Our results can be used in comparative anatomy studies of pancreas in mammals.

Mobilization and Rupture of LNAPL Ganglia during Freeze-Thaw: Two-Dimensional Cell Experiments

Experiments were conducted on dodecane at residual saturation (21-26%) in a two-dimensional water-saturated glass bead cell (0.5 mm diameter)--to simulate light nonaqueous phase liquid (LNAPL) trapped below the water table--subject to controlled freeze-thaw cycles. The experiments reveal substantial remobilization and rupture of LNAPL ganglia during freeze-thaw, especially during the first few cycles. This includes the detachment and upward mobilization of LNAPL from larger ganglia during upward propagation of the freezing front; the formation of numerous subsinglet ganglia during this transport process, and their entrapment in ice; and the coalescence of such small ganglia during thawing, to form larger singlets. Theoretical calculations suggest that the LNAPL redistribution is caused by large freezing-induced pressure gradients, of up to 6 orders of magnitude higher than the water-LNAPL interfacial (capillary) pressure. The findings have important implications for the understanding and remediation of LNAPLs in cold climate regions.

Ganglion cell density and oil droplet distribution in the retina of brown-eared bulbul (Hysipetes amaurotis)

This study was intended to determine the number and density of both retinal ganglion cells and the oil droplets of cone photoreceptor cells in brown-eared bulbul (Hypsipetes amaurotis). For this study birds were killed with proper dose of anesthetic (pentobarbital, 30 mg/kg), and the eyes were removed from the orbital cavity to isolate the retina. For the ganglion cell study retinal whole-mount specimens were prepared and stained with 0.1% cresyl violet. The different types of oil droplets were counted from color microphotographs of freshly prepared retinal samples. The mean total number of ganglion cells was estimated at approximately 2.5 x 10(6); with an average density of 16 523 cells/mm(2). Two high-density areas, namely the central area (CA) and the dorso-temporal area (DTA), are located in the central and dorso-temporal retinas, respectively, in bulbuls (24 032 cells/mm(2) in the CA; 23 113 cells/mm(2) in the DTA). Small ganglion cells persisted in the highest density areas, whereas the largest soma sizes were found in the lowest density areas of the retina. Four types of different colored oil droplets - red, orange, green and clear - were identified with an average density of 29 062/mm(2). Among the different colors, the green oil droplets had a significantly higher population (13 083/mm(2)) than the others across the retina. The central retina had a significantly higher number of all types of oil droplets, at a density of 60 552/mm(2). The density and size of the different colored oil droplets were inversely related across the regions of the retina. Taken together, it is concluded that the CA of the retina is an excellent quality area for visual perception due to peak density of ganglion cells and oil droplets. Moreover, each specific oil droplet makes a distinct contribution to visual perception, thereby ensuring that the bird has a retina that best matches its natural environment and feeding behavior.

Regional specialization of the Tree Sparrow Passer montanus retina: ganglion cell density and oil droplet distribution

ABSTRACT The purpose of this study was to define the number and density of both retinal ganglion cells and the oil droplets of cone photoreceptor cells in the Tree Sparrow Passer montanus. Retinal whole-mount specimens were prepared and stained with 0.1% cresyl violet for the ganglion cell study, and fresh retinal samples were subjected to color microphotography for the oil droplet study. The mean total number of ganglion cells was estimated at approximately 1.6×5106; with an average density of 18,539/mm2. The density of the ganglion cells peaked in the area centralis, at 26,000 cells/mm2, and gradually decreased with retinal eccentricity. Small ganglion cells persisted in the highest density areas, whereas the largest soma sizes were found in the lowest density areas of the retina. Four types of different colored oil droplets—red, yellow, green and clear—were identified with an average density of 25,680/mm2. Among the different colors, the green oil droplets showed a significantly higher density (12,247/...

Topography of ganglion cells in the retina of the duck (Anas platyrhynchos var. domesticus)

ABSTRACTThe purpose of this study was to define ganglion cell density, size and topography in the retina of the mallard duck. After killing adult mallard ducks (Anas platyrhynchos var. domesticus), their eyes were removed using pentobarbital (30 mg/kg). The retinas were isolated, whole mount specimens were prepared by staining with 0.1% cresyl violet and then fixing the tissues for study. The retinal ganglion cells were counted, mapped and measured. The mean total number of ganglion cells was estimated at approximately 1.7 × 106 and the retinal area centralis had the highest ganglion cell density with 15 820 cells/mm2. The number of ganglion cell bodies was highest in the temporal area, followed by the nasal, dorsal and ventral areas. Ganglion cell size ranged from 56 to 406 μm2. A population of small ganglion cells persisted into the central area just above the optic disc and the largest soma area was in the ventral zone of the retina. This localization of ganglion cells suggests that the quality of vision is not equal in all the areas of the duck retina and the central part may have the highest vision quality as a function of the retinal ganglion cells.

Carotid body-like tissues around the rat posterior cricoarytenoid muscle

We examined the carotid body-like tissues around the posterior cricoarytenoid (PCA) muscle of the rat by light and electron microscopy. One branch after bifurcation of the inferior (recurrent) laryngeal nerve frequently formed a small ganglion at the lateral side of this muscle and sometimes contained paraganglion cells (granule-containing cells). In addition, encapsulated structures (paraganglia) enveloped by a few layer of capsular cells were often observed on and near the muscle. Moreover, granule-containing cells resembling the encapsulated paraganglion cells were found in clusters outside the small nerve. These clustered cells were incompletely surrounded by fibroblastic processes. In addition to synapses between adjacent cells, afferent and efferent synapses were distinguished between nerve endings and these cells, possibly receiving both afferent and efferent innervation. These findings suggest that the clustered granule-containing cells outside the small nerve in the proximity of the PCA muscle may function as chemoreceptor cells as well as the paraganglion cells within the nerve bundles and the encapsulated paraganglia.

Transforming growth factor beta mediates apoptosis in the ganglion cell layer during all programmed cell death periods of the developing murine retina

Transforming growth factor beta (TGF-β) is an extracellular signaling molecule known to mediate programmed cell death (PCD) in the developing retina. In the present study, we investigated the expression profiles and activity levels of TGF-β ligand and TGF-β receptors (TβR) during the successive physiological PCD periods of the developing postnatal mouse retina. The peak of TβR expression levels – revealed by Western Blots and MLEC assays – coincided with the main periods of postnatal (P) retinal murine PCD at P2, P9, and P15. Immunocytochemical studies showed that the localization of the TβRs is restricted to the ganglion cell layer. Application of a neutralizing anti-TGF-β antibody to E15 and P9 retinal cultures resulted in a significant decrease in the number of TUNEL-positive neurons specifically in the ganglion cell or prospective ganglion cell layer. Treatment of P2 and P15 organotypic murine retinal wholemount cultures with exogenous recombinant TGF-β significantly increased cell death levels. In the P15 retina, where PCD affects ganglion cells and photoreceptors, TGF-β induced cell death of large retinal ganglion cells, whereas small ganglion cells and photoreceptor neurons remained unaffected. Our data indicate that TGF-β mediated apoptosis during all postnatal retinal PCD phases specifically affects the fate of retinal ganglion cells.

Increase of Galanin in Trigeminal Ganglion during Tooth Movement

It is known that nerve fibers containing neuropeptides such as galanin increase in the periodontal ligament during experimental tooth movement. However, the origin of galanin-containing nerve fibers in the periodontal ligament remains unclear. This study was conducted to examine our hypothesis that the increased galanin nerve fibers have a sensory neuronal origin, and that the peptide is associated with pain transmission and/or periodontal ligament remodeling during experimental tooth movement. In control rats, galanin-immunoreactive trigeminal ganglion cells were very rare and were observed predominantly in small ganglion cells. After 3 days of experimental tooth movement, galanin-immunoreactive trigeminal ganglion cells significantly increased, and the most marked increase was observed at 5 days after experimental tooth movement. Furthermore, their cell size spectrum also significantly changed after 3 and 5 days of movement: Medium-sized and large trigeminal ganglion cells began expressing, and continued to express, galanin until 14 days after experimental tooth movement. These findings suggest that the increase of galanin in the periodontal ligament during experimental tooth movement at least partially originates from trigeminal ganglion neurons and may play a role in pain transmission and/or periodontal remodeling.

Effect of protein kinase C?? inhibitor on Ca2+ homeostasis in diabetic sensory neurons

To elucidate the direct effect of selective protein kinase Cbeta inhibitor LY333531 on diabetic sensory neurons, we examined intracellular Ca(2+) concentration in isolated rat dorsal root ganglion neurons using the fluorescent Ca(2+) indicator fura-2. The duration of calcium transients induced by high (50 mM) extracellular K in small diabetic dorsal root ganglion neurons was significantly prolonged compared with that in control neurons. This prolonged intracellular Ca concentration elevation in diabetic neurons was normalized rapidly and reversibly by LY333531 in a dose-dependent manner, and the effect of LY333531 was completely abolished by pretreating the neurons with mitochondrial calcium uniporter inhibitor, Ruthenium 360. These results suggest that LY333531 has an ameliorating effect on calcium homeostasis of diabetic sensory neurons via mitochondrial calcium buffering.