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Background: This study aims to revisit the anatomy of orbital segment of the third cranial nerve (CN III). The study also involved morphometric measurements of CN III muscular branches. Detailed description of observed anatomical variations and their incidence was also included. The study supplements earlier findings with detailed observations of the neuromuscular relations. Materials and methods: The study was conducted on 52 orbits taken from 26 cadaveric heads (10 males and 16 females; Central European population). Results: Anatomical variations of the orbital segment of the CN III observed on the examined material involved both the superior and inferior branch of this nerve. The muscular branch innervating the levator palpebrae superioris muscle occasionally pierces the superior rectus muscle. The nerve to the inferior oblique muscle may pierce and innervate the inferior rectus muscle. In rare instances, duplication of the parasympathetic root of the ciliary ganglion may also occur. Among the muscular branches, the smallest diameter reached the branch to the levator palpebrae superioris muscle. Among the three muscular branches derived from the inferior branch of the CN III, the nerve to the inferior oblique was the longest one. Its length varied from 28.9 mm to 37.4 mm. The shortest was the muscular branch to the inferior rectus muscle. Its length varied from 0 mm (when muscular sub-branches arose directly from the nerve to the inferior oblique muscle) to 7.58 mm. Conclusions: This study presented the characteristic of orbital segment of the CN III, including anatomical variations and morphometric measurements relevant to intraorbital procedures.

The centrally projecting Edinger-Westphal nucleus (EWcp) is a midbrain neuronal group, adjacent but segregated from the preganglionic Edinger-Westphal nucleus that projects to the ciliary ganglion. The EWcp plays a crucial role in stress responses and in maintaining energy homeostasis under conditions that require an adjustment of energy expenditure, by virtue of modulating heart rate and blood pressure, thermogenesis, food intake, and fat and glucose metabolism. This modulation is ultimately mediated by changes in the sympathetic outflow to several effector organs, including the adrenal gland, heart, kidneys, brown and white adipose tissues and pancreas, in response to environmental conditions and the animal’s energy state, providing for appropriate energy utilization. Classic neuroanatomical studies have shown that the EWcp receives inputs from forebrain regions involved in these functions and projects to presympathetic neuronal populations in the brainstem. Transneuronal tracing with pseudorabies virus has demonstrated that the EWcp is connected polysynaptically with central circuits that provide sympathetic innervation to all these effector organs that are critical for stress responses and energy homeostasis. We propose that EWcp integrates multimodal signals (stress, thermal, metabolic, endocrine, etc.) and modulates the sympathetic output simultaneously to multiple effector organs to maintain energy homeostasis under different conditions that require adjustments of energy demands.

Tonic pupil, or Adie’s pupil, is an autonomic disorder due to a loss of function of parasympathetic ciliary ganglion cells. Upon examination, the pupil appears tonically dilated and shrinks poorly to light, while reacting better to accommodation stimulus. The denervated iris sphincter is very sensitive to topical parasympathomimetic pilocarpine drops. Indeed, if Adie is present, the dilated pupil will constrict more than the normal pupil. Most cases are idiopathic or due to a viral infection and have a benign course. They usually occur in women between 20 and 40 years of age. Other reported causes of tonic pupils can be vascular, traumatic, inflammatory, paraneoplastic, and neoplastic. Breast cancer generally metastasizes to the brain in advanced stages and orbital localizations have sometimes been reported. In our case, a meningeal and retro-orbit cancer invasion caused a dysfunction of the parasympathetic fibers which lead to the pupil through the optical foramen. Indeed, first ophthalmic symptoms were only an enlarged pupil poorly responsive to light. This unusual clinical sign led to the discovery of an unknown breast cancer in an advanced stage. In young adult women, unilateral tonic pupils are considered a benign parasympathetic ocular disorder that is rarely observed in clinical practice. However, it can be found in numerous systemic diseases; thus instrumental and laboratory findings are mandatory. Tumors can also represent etiologic agents and secondary localizations from breast cancer to extra parenchymal CNS structures should be considered in differential diagnosis hypothesis.

In chicks, axial length and choroidal thickness undergo circadian oscillations. The choroid is innervated by both branches of the autonomic nervous system, but their contribution(s) to these rhythms is unknown. We used two combination lesions to test this. For parasympathectomy, nerve VII was sectioned presynaptic to the pterygopalatine ganglia, and the ciliary post-ganglionics were cut (double lesion; n = 8). Triple lesions excised the sympathetic superior cervical ganglion as well (n = 8). Sham surgery was done in controls (n = 7). 8–14 days later, axial dimensions were measured with ultrasonography at 4-h intervals over 24 h. Rhythm parameters were assessed using a “best fit” function, and growth rates measured. Both types of lesions resulted in ultradian (> 1 cycle/24 h) rhythms in choroidal thickness and axial length, and increased vitreous chamber growth (Exp-fellow: double: 69 µm; triple: 104 µm; p

The pupil is actually a hole within the iris with innervation as part of the visual pathway and cranial nerve three (aka. oculomotor nerve), but due to its anatomical and pathological peculiarities, it was separated in a stand-alone chapter. Exams usually include 2–3 questions from this chapter, where a question on pupillary reflux and the impact of different lesions almost always present. An example of such questions is asking about the impact of a lesion at the ciliary ganglion on the pupillary response, where such lesions will cause a weak direct light response, with dilated pupil ipsilateral to the lesion, and intact consensual light reflex.

Cranial nerves are closely related to the eye, where cranial nerves 3, 4, and 6 are related to eye and lid movements, cranial nerve 5 to eye sensations, and cranial nerve 7 to lid movement and lacrimal gland supply. Ophthalmology exams may include around 10 questions on topics related to cranial nerves, including their origin, synapses, organs supplied, nuclei, and ganglia among others. An example of such questions is asking about nerves synapsing at ciliary ganglion, where despite having parasympathetic, sympathetic, and sensory nerves passing through the ganglion, only parasympathetic nerves synapse there.

An initial step in the evaluation of anisocoria is assessing the pupillary light reflex. If a pupil is not responsive to light, then the near pupillary reflex needs to be evaluated. Unilateral light-near pupil dissociation occurs due to a lesion of the ciliary ganglion, postganglionic parasympathetic pathway, retina, or optic nerve.

Chick ciliary ganglia (CG) are part of the parasympathetic nervous system and are responsible for the innervation of the muscle tissues present in the eye. This ganglion is constituted by a homogenous population of ciliary and choroidal neurons that innervate striated and smooth muscle fibers, respectively. Each of these neuronal types regulate specific eye structures and functions. Over the years, neuronal cultures of the chick ciliary ganglia were shown to be effective cell models in the study of muscle-nervous system interactions, which communicate through cholinergic synapses. Ciliary ganglion neurons are, in its majority, cholinergic. This cell model has been shown to be useful comparatively to previously used heterogeneous cell models that comprise several neuronal types, besides cholinergic. Anatomically, the ciliary ganglion is localized between the optic nerve (ON) and the choroid fissure (CF). Here, we describe a detailed procedure for the dissection, dissociation and in vitro culture of ciliary ganglia neurons from chick embryos. We provide a step-by-step protocol in order to obtain highly pure and stable cellular cultures of CG neurons, highlighting key steps of the process. These cultures can be maintained in vitro for 15 days and, hereby, we show the normal development of CG cultures. The results also show that these neurons can interact with muscle fibers through neuro-muscular cholinergic synapses.

A tonic pupil, without other features of an oculomotor neuropathy, is due to a lesion in the ciliary ganglion or short ciliary nerves. Here, we present a case of a tonic pupil in a woman with radiation-treated adenoid cystic carcinoma of the nasopharynx with perineural spread and skull base involvement. This a rare case of a tonic pupil caused by direct invasion of the ciliary ganglion or postradiation effects.

The autonomic innervation in the anterior chamber (AC) structures might play an efferent role in neural intraocular pressure (IOP) regulation, the center of which is thought to be located in the hypothalamus. In this study, we identified the efferent pathway from the hypothalamus to the autonomic innervation in the AC structures. Retrograde trans-multisynaptic pseudorabies virus (PRV) expressing green or red fluorescent protein, PRV531 and PRV724, was injected into the right and left AC of five rats, respectively; PRV531 was injected into the right AC of another five rats, and a non-trans-synaptic tracer, FAST Dil, was injected into the right AC of five rats as a control. Fluorescence signals in autonomic ganglia,the spinal cord and the central nervous system (CNS) were observed. Seven days after FAST Dil right AC injection, FAST Dil-labeled neurons were observed in the ipsilateral autonomic ganglia, including the superior cervical ganglion, pterygopalatine ganglion, and ciliary ganglion, but not in the CNS. Four and a half days after PRV531 injection into the right AC, PRV531-labeled neurons could be observed in the ipsilateral autonomic ganglia and bilateral hypothalamus nuclei, especially in the suprachiasmatic nucleus, paraventricular nucleus, dorsomedial hypothalamus, perifornical hypothalamus and ventral mammillary nucleus. Fluorescence signals of PRV531 mainly located in the ipsilateral autonomic preganglionic nuclei (Edinger-Westphal nucleus, superior salivatory nucleus and intermediolateral nucleus), but not in sensory trigeminal nuclei. Four and a half days after PRV531 right AC injection and PRV724 left AC injection, PRV531-labeled, PRV724-labeled, and double-labeled neurons could be observed in the above mentioned bilateral hypothalamus nuclei; but few contralateral infection-involving neurons (including double-labeled neurons) could be detected in the autonomic preganglionic nuclei. Our results indicate that there exist a both crossed and uncrossed hypothalamo-pre-parasympathetic and -pre-sympathetic tracts in the efferent pathways between the bilateral hypothalamic nuclei and the autonomic innervation of the bilateral AC.

The centrally-projecting Edinger−Westphal nucleus (EWcp) is a brain region distinct from the preganglionic Edinger−Westphal nucleus (EWpg). In contrast to the EWpg, the EWcp does not send projections to the ciliary ganglion and appears not to regulate oculomotor function. Instead, evidence is accumulating that the EWcp is extremely sensitive to alcohol and several other drugs of abuse. Studies using surgical, genetic knockout, and shRNA approaches further implicate the EWcp in the regulation of alcohol sensitivity and self-administration. The EWcp is also known as the site of preferential expression of urocortin 1, a peptide of the corticotropin-releasing factor family. However, neuroanatomical data indicate that the EWcp is not a monotypic brain region and consists of several distinct subpopulations of neurons. It is most likely that these subpopulations of the EWcp are differentially involved in the regulation of actions of addictive drugs. This review summarizes and analyzes the current literature of the EWcp’s involvement in actions of drugs of abuse in male and female subjects in light of the accumulating evidence of complexities of this brain region.

The vertebrate ciliary ganglion (CG) is a relay station in the parasympathetic pathway activating the iris sphincter and ciliary muscle to mediate pupillary constriction and lens accommodation, respectively. While the postganglionic motoneurons in the CG are cholinergic, as are their inputs, there is evidence from avian studies that GABA may also be involved. Here, we used light and electron microscopic methods to examine the GABAergic innervation of the CG in Macaca fascicularis monkeys. Immunohistochemistry for the gamma aminobutyric acid synthesizing enzyme glutamic acid decarboxylase (GAD) and choline acetyltransferase (ChAT) revealed that all CG neurons are contacted by ChAT-positive terminals. A subpopulation of 17.5% of CG neurons was associated with terminal boutons expressing GAD-immunoreactivity in addition. Double-labeling for GAD and synaptophysin confirmed that these were synaptic terminals. Electron microscopic analysis in conjunction with GABA-immunogold staining showed that (1) GAD-positive terminals mainly target dendrites and spines in the perisomatic neuropil of CG neurons; (2) GABA is restricted to a specific terminal type, which displays intermediate features lying between classically excitatory and inhibitory endings; and (3) if a CG neuron is contacted by GABA-positive terminals, virtually all perisomatic terminals supplying it show GABA immunoreactivity. The source of this GABAergic input and whether GABA contributes to a specific CG function remains to be investigated. Nevertheless, our data indicate that the innervation of the ciliary ganglion is more complex than previously thought, and that GABA may play a neuromodulatory role in the control of lens or pupil function. J. Comp. Neurol. 525:1517-1531, 2017. © 2016 Wiley Periodicals, Inc.

Herpes simplex virus type I (HSV-1) infection causes inflammation in the cornea known as herpes simplex virus keratitis (HSK), a common but serious corneal disease. It is not entirely clear whether the virus during recurring infection comes from the trigeminal ganglia or the eye tissue, including the retina and ciliary ganglion. Because the tree shrew is closely related to primates and tree shrew eye anatomic structures are similar to humans, we studied HSV-1 corneal infection in the tree shrew. We found that HSK symptoms closely mimic those found in human HSK showing typical punctiform and dendritic viral keratitis during the acute infection period. Following the HSV-specific lesions, complications such as stromal scarring, corneal thickening (primary infection), opacity, and neovascularization were observed. In the tree shrew model, following ocular inoculation, the cornea becomes infected, and viral protein can be detected using anti-HSV-1 antibodies in the epithelial layer and retina neuronal ganglion cells. The HSV-1 transcripts, ICP0, ICP4, and LAT can be detected at 3 days post-infection (dpi), peaking at 5 dpi. After 2 weeks, ICP4 and ICP0 transcripts are reduced to a basal level, but the Latency Associated Transcripts (LATs) continue to accumulate. Interestingly, after the acute infection, we still detected abundant active HSV-1 in tree shrew eyes. Further, we found HSV-1 persistent in the ciliary ganglion and cornea. These findings are discussed in support of the tree shrew as a non-human primate HSK model, which could be useful for mechanistic studies of HSK.

Background: Ciliary ganglion (CG) can be easily injured without notice in many intraorbital procedures. Surgical procedures approaching the lateral side of the orbit are at risk of CG injury which results in transient mydriasis and tonic pupil. This study aims to focus on the morphometric study of the CG which is pertinent to intraoperative procedure. Materials and methods: Forty embalmed cadaveric globes were dissected to observe the location, shape and size of CG, characteristics and number of roots reaching CG, number of short ciliary nerve in the orbit. Distances from CG to posterior end of globe, optic nerve, lateral rectus muscle and its scleral insertion were measured. Results: Ciliary ganglion was located between optic nerve and lateral rectus in every case. Its shape could be oval, round and irregular. Mean width of CG was 2.24 mm and mean length was 3.50 mm. Concerning the roots, all 3 roots were present in 29 (72.5%) cases. Absence of motor root was found in 7 (17.5%) cases. Absence of sympathetic root was found in 4 (5%) cases. The number of motor root could be 1, 2 and also 3 roots. Three motor roots were found in 1 case which originated from nerve to inferior oblique muscle. Only one sensory root was found in every specimen. One sympathetic root could be observed in most of the specimens and 6–14 short ciliary nerves were found. Mean distances from CG to posterior end of globe, optic nerve, lateral rectus muscle and its scleral insertion were 16.04 mm, 1.47 mm, 2.88 mm, and 31.53 mm, respectively. Conclusions: This study described the characteristic of CG, number of its nerve root and some measurements relevant to intraorbital procedures in Asian population. Moreover, a new parameter was the distance between CG and scleral insertion of the lateral rectus muscle. This parameter should be considered when performing operation involved the lateral rectus muscle and BTX-A injection to lateral rectus muscle to reduce CG injury.

The motor outflow for the pupillary light reflex originates in the preganglionic motoneuron subdivision of the Edinger–Westphal nucleus (EWpg), which also mediates lens accommodation. Despite their importance for vision, the morphology, ultrastructure and luminance-related inputs of these motoneurons have not been fully described in primates. In macaque monkeys, we labeled EWpg motoneurons from ciliary ganglion and orbital injections. Both approaches indicated preganglionic motoneurons occupy an EWpg organized as a unitary, ipsilateral cell column. When tracers were placed in the pretectal complex, labeled terminals targeted the ipsilateral EWpg and reached contralateral EWpg by crossing both above and below the cerebral aqueduct. They also terminated in the lateral visceral column, a ventrolateral periaqueductal gray region containing neurons projecting to the contralateral pretectum. Combining olivary pretectal and ciliary ganglion injections to determine whether a direct pupillary light reflex projection is present revealed a labeled motoneuron subpopulation that displayed close associations with labeled pretectal terminal boutons. Ultrastructurally, this subpopulation received synaptic contacts from labeled pretectal terminals that contained numerous clear spherical vesicles, suggesting excitation, and scattered dense-core vesicles, suggesting peptidergic co-transmitters. A variety of axon terminal classes, some of which may serve the near response, synapsed on preganglionic motoneurons. Quantitative analysis indicated that pupillary motoneurons receive more inhibitory inputs than lens motoneurons. To summarize, the pupillary light reflex circuit utilizes a monosynaptic, excitatory, bilateral pretectal projection to a distinct subpopulation of EWpg motoneurons. Furthermore, the interconnections between the lateral visceral column and olivary pretectal nucleus may provide pretectal cells with bilateral retinal fields.

The ciliary ganglion is of outmost physiological importance, due to its involvement in pupillary light reflex circuits. The ciliary ganglion may be damaged during surgical procedures. Therefore, the aim of the study was to examine the anatomical variations of the ganglion with an emphasis in location in the orbit. Anatomical variations of the parasympathetic root of the ganglion were also examined and classified. 40 orbits were dissected. The orbital content was removed en bloc. The lateral rectus muscle was detached from its insertion and reflected. After the removal of the orbital fat, the ciliary ganglion was visualized. Then, the morphology, roots and location of the ganglion were assessed. The location of the ciliary ganglion varied from 17 to 83.7% (mean = 51.4%, median = 53%, SD 14.8%) of the distance between the point of the optic nerve emerging from the eyeball and the common tendinous ring (counting from the front). In most cases (55%) it was found between 50.1 and 75% of the distance between the back of the eye and the common tendinous ring, while in 37.5% of cases it was found between 25 and 50% of this distance. The parasympathetic root of the ciliary ganglion was variable. Its origin was from the nerve to the inferior oblique muscle in most of cases. In four cases (10%), the parasympathetic root of the ciliary ganglion was duplicated. The ciliary ganglion occupies a variable position with regards to the optic nerve. The parasympathetic root of the ganglion may be unusually short or doubled.

Severe bilateral mydriasis and bilaterally decreased vision were observed in a 23-year-old crossbred warmblood gelding with a history of pituitary pars intermedia dysfunction. Ten years after the onset of clinical signs, it was killed humanely because of worsening of clinical signs and loss of therapeutic responsiveness. Postmortem examination of the head was performed to confirm the suspected pituitary neoplasm and to investigate secondary oculomotor lesions. Pathomorphologic examination revealed an expansile space-occupying pituitary adenoma and degenerative changes in the preganglionic oculomotor nerve, ciliary ganglion, and optic chiasm. The ocular clinical findings share features of a cavernous sinus syndrome.

The functions of the eye are regulated by and dependent upon the autonomic nervous system. The parasympathetic nervous system controls constriction of the iris and accommodation of the lens via a pathway with preganglionic motor neurons in the Edinger-Westphal nucleus and postganglionic motor neurons in the ciliary ganglion. The parasympathetic nervous system regulates choroidal blood flow and the production of aqueous humor through a pathway with preganglionic motor neurons in the superior salivatory nucleus and postganglionic motor neurons in the pterygopalatine (sphenopalatine) ganglion. The sympathetic nervous system controls dilation of the iris and may modulate the outflow of aqueous humor from the eye. The sympathetic preganglionic motor neurons lie in the intermediolateral cell column at the first level of the thoracic cord, and the postganglionic motor neurons are found in the superior cervical ganglion. The central pathways controlling different autonomic functions in the eye are found in a variety of locations within the central nervous system. The reflex response of the iris to changes in luminance levels begins with melanopsin-containing retinal ganglion cells in the retina that project to the olivary pretectal nucleus. This nucleus then projects upon the Edinger-Westphal preganglionic motoneurons. The dark response that produces maximal pupillary dilation involves the sympathetic pathways to the iris. Pupil size is also regulated by many other factors, but the pathways to the parasympathetic and sympathetic preganglionic motoneurons that underlie this are not well understood. Lens accommodation is controlled by premotor neurons located in the supraoculomotor area. These also regulate the pupil, and control vergence angle by modulating the activity of medial rectus, and presumably lateral rectus, motoneurons. Pathways from the frontal eye fields and cerebellum help regulate their activity. Blood flow in the choroid is regulated with respect to systemic blood pressure through pathways through the nucleus of the tractus solitarius. It is also regulated with respect to luminance levels, which likely involves the suprachiasmatic nucleus, which receives inputs from melanopsin-containing retinal ganglion cells, and other areas of the hypothalamus that project upon the parasympathetic preganglionic neurons of the superior salivatory nucleus that mediate choroidal vasodilation.

The calyx-type synapse is a giant synaptic structure in which a presynaptic terminal wraps around a postsynaptic neuron in a one-to-one manner. It has been used for decades as an experimental model system of the synapse due to its simplicity and high accessibility in physiological recording methods. In particular, the calyx of the embryonic chick ciliary ganglion (CG) has enormous potential for synapse science because more flexible genetic manipulations are available compared with other synapses. Here, we describe methods to study presynaptic morphology, physiology, and development using CGs and cutting-edge molecular tools. We outline step-by-step protocols for presynaptic gene manipulation using in ovo electroporation, preparation of isolated CGs, 3-D imaging for single-axon tracing in transparent CGs, electrophysiology of the presynaptic terminal, and an all-optical approach using optogenetic molecular reagents. These methods will facilitate studies of the synapse and neuronal circuits in the future. © 2019 by John Wiley & Sons, Inc.

Avian ciliary ganglion (CG) development involves a transient execution phase of apoptosis controlling the final number of neurons, but the time-dependent molecular mechanisms for neuronal cell fate are largely unknown. To elucidate the molecular networks regulating important aspects of parasympathetic neuronal development, a genome-wide expression analysis was performed during multiple stages of avian CG development between embryonic days E6 and E14. The transcriptome data showed a well-defined sequence of events, starting from neuronal migration via neuronal fate cell determination, synaptic transmission, and regulation of synaptic plasticity to growth factor associated signaling. In particular, we extracted a neuronal apoptosis network that characterized the cell death execution phase at E8/E9 and apoptotic cell clearance at E14 by combining the gene time series analysis with network synthesis from the chicken interactome. Network analysis identified TP53 as key regulator and predicted involvement of the BH3 interacting domain death agonist (BID). A virus-based RNAi knockdown approach in vivo showed a crucial impact of BID expression on the execution of ontogenetic programmed cell death (PCD). In contrast, Bcl-XL expression did not impact PCD. Therefore, BID-mediated apoptosis represents a novel cue essential for timing within CG maturation.

In the case of anatomical dissection as part of medical education, it is difficult for medical students to find the ciliary ganglion (CG) since it is small and located deeply in the orbit between the optic nerve and the lateral rectus muscle and embedded in the orbital fat. Here, we would like to introduce simple ways to find the CG by 1): tracing the sensory and parasympathetic roots to find the CG from the superior direction above the orbit, 2): transecting and retracting the lateral rectus muscle to visualize the CG from the lateral direction of the orbit, and 3): taking out whole orbital structures first and dissecting to observe the CG. The advantages and disadvantages of these methods are discussed from the standpoint of decreased laboratory time and students as beginners at orbital anatomy.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide found at synapses throughout the central and autonomic nervous system. We previously found that PACAP engages a selective G-protein coupled receptor (PAC1R) on ciliary ganglion neurons to rapidly enhance quantal acetylcholine (ACh) release from presynaptic terminals via neuronal nitric oxide synthase (NOS1) and cyclic AMP/protein kinase A (PKA) dependent processes. Here, we examined how PACAP stimulates NO production and targets resultant outcomes to synapses. Scavenging extracellular NO blocked PACAP-induced plasticity supporting a retrograde (post- to presynaptic) NO action on ACh release. Live-cell imaging revealed that PACAP stimulates NO production by mechanisms requiring NOS1, PKA and Ca(2+) influx. Ca(2+)-permeable nicotinic ACh receptors composed of α7 subunits (α7-nAChRs) are potentiated by PKA-dependent PACAP/PAC1R signaling and were required for PACAP-induced NO production and synaptic plasticity since both outcomes were drastically reduced following their selective inhibition. Co-precipitation experiments showed that NOS1 associates with α7-nAChRs, many of which are perisynaptic, as well as with heteromeric α3*-nAChRs that generate the bulk of synaptic activity. NOS1-nAChR physical association could facilitate NO production at perisynaptic and adjacent postsynaptic sites to enhance focal ACh release from juxtaposed presynaptic terminals. The synaptic outcomes of PACAP/PAC1R signaling are localized by PKA anchoring proteins (AKAPs). PKA regulatory-subunit overlay assays identified five AKAPs in ganglion lysates, including a prominent neuronal subtype. Moreover, PACAP-induced synaptic plasticity was selectively blocked when PKA regulatory-subunit binding to AKAPs was inhibited. Taken together, our findings indicate that PACAP/PAC1R signaling coordinates nAChR, NOS1 and AKAP activities to induce targeted, retrograde plasticity at autonomic synapses. Such coordination has broad relevance for understanding the control of autonomic synapses and consequent visceral functions.

This the case of a 6 year old with segmental hypohidrosis in the right side of his body, ipsilateral tonic pupil and hiporreflexia. This triad leads to the clinical diagnosis of the Ross Syndrome. The relevance of this case is the recognition of the hypohidrosis as a sign of an autonomic disorder. The Ross syndrome is a progressive benign autonomic disorder, the pathophysiology is the denervation of parasympathetic postganglionic cholinergic fibers between the ciliary ganglion and iris (pupil tonic), presynaptic degeneration of dorsal root fibers (hyporeflexia) and degeneration of the postganglionic sweat glands fibers. The cause is unclear. The course is chronic, with variable extension of the hypohidrosis. Patients may get compromise of thermoregulation and impaired quality of life, that is why the patients and caregivers should be warning and learn the strategies to avoid body overheating.

Preganglionic motoneurons supplying the ciliary ganglion control lens accommodation and pupil diameter. In cats, these motoneurons make up the preganglionic Edinger-Westphal population, which lies rostral, dorsal and ventral to the oculomotor nucleus. A recent cat study suggested that caudal motoneurons control the lens and rostral motoneurons control the pupil. This led us to examine the morphology, ultrastructure and pretectal inputs of these populations. Preganglionic motoneurons retrogradely labeled by introducing tracer into the cat ciliary ganglion generally fell into two morphologic categories. Fusiform neurons were located rostrally, in the anteromedian nucleus and between the oculomotor nuclei. Multipolar neurons were found caudally, dorsal and ventral to the oculomotor nucleus. The dendrites of preganglionic motoneurons within the anteromedian nucleus crossed the midline, providing a possible basis for consensual responses. Ultrastructurally, several different classes of synaptic profiles contact preganglionic motoneurons, suggesting their activity may be modified by a variety of inputs. Furthermore, there were differences between the synaptic populations contacting the rostral and caudal populations, supporting the contention that these populations display functional differences. Anterogradely labeled pretectal terminals were observed in close association with labeled preganglionic motoneurons, particularly in the rostral population. Ultrastructural analysis revealed that these terminals, packed with clear, spherical vesicles, made asymmetric synaptic contacts onto motoneurons in the rostral population indicating these cells serve the pupillary light reflex. Thus, the preganglionic motoneurons found in the cat display morphologic, ultrastructural and connectional differences suggesting that this rostral preganglionic population is specialized for pupil control, while more caudal elements control the lens.

BACKGROUND: Requirement of the good specimens of human eye showing all its muscles from their origin to insertion, optic nerve and ciliary ganglion has been always felt during the teaching of anatomy of human eye. AIM: To make Museum specimens of human eye showing eye ball with its muscles, nerves, vessels, ciliary ganglion and optic nerve for teaching of surgical and gross anatomy. These specimens may help in formation of better eye prosthesis used in the field of ophthalmic plastic surgeries. MATERIAL AND METHOD: Five cadavers were marked for procurement of specimens during routine dissection in dissection hall by undergraduates. Cranial vault and brain were already removed. Roof of orbit were removed by superior approach with preservation of apex with cone of muscles and optic nerve. Removal of superciliary arch with frontal approach was followed to obtain complete eye ball and other structures. Fine dissection was performed to clean the area for demonstration. Specimens were mounted by Kaiserling's technique in glass jars. RESULT: By this method ten specimens of eye were mounted showing all muscles with their origin and insertion, their nerve supply, optic nerve, ophthalmic artery and its branch entering into optic nerve in different views of different specimens. CONCLUSION: Ten specimens were procured from five cadavers dissected routinely in dissection hall by undergraduates. These specimens are providing a very good 3- dimensional view of eye and related structures. An interactive method of teaching using prosected specimens is raising a good satisfactory level among students.

The research was performed on 16 one-year-old domestic turkeys of Beltsville race and 16 domestic ducks of the Pekinese race, of both sexes. Standard histological technique was used and morphometric analysis was performed using histological samples. Ciliary ganglion morphometric analysis revealed the presence of two cell populations of ganglionic neurocytes: choroid and ciliary cells, clearly differing in diameter. Ciliary cells were predominant in turkeys, whereas choroid cells in ducks. The statistical analysis showed that the diameter and surface area of ganglionic neurocytes, the diameter and cross sectional area through the ciliary ganglion, as well as, the number of ganglionic cells on the cross-section through the ganglion were significantly larger (P

During a certain critical period in the development of the central and peripheral nervous systems, axonal branches and synapses are massively reorganized to form mature connections. In this process, neurons search their appropriate targets, expanding and/or retracting their axons. Recent work suggested that the caspase superfamily regulates the axon morphology. Here, we tested the hypothesis that caspase 3, which is one of the major executioners in apoptotic cell death, is involved in regulating the axon arborization. The embryonic chicken ciliary ganglion was used as a model system of synapse reorganization. A dominant negative mutant of caspase-3 precursor (C3DN) was made and overexpressed in presynaptic neurons in the midbrain to interfere with the intrinsic caspase-3 activity using an in ovo electroporation method. The axon arborization pattern was 3-dimensionally and quantitatively analyzed in the ciliary ganglion. The overexpression of C3DN significantly reduced the number of branching points, the branch order and the complexity index, whereas it significantly elongated the terminal branches at E6. It also increased the internodal distance significantly at E8. But, these effects were negligible at E10 or later. During E6-8, there appeared to be a dynamic balance in the axon arborization pattern between the "targeting" mode, which is accompanied by elongation of terminal branches and the pruning of collateral branches, and the "pathfinding" mode, which is accompanied by the retraction of terminal branches and the sprouting of new collateral branches. The local and transient activation of caspase 3 could direct the balance towards the pathfinding mode.

Autonomic dysfunction can be associated with pupillary abnormalities. We describe a rare association of tonic pupils, congenital central hypoventilation syndrome, and Hirschsprung disease in a newborn with a mutation in the PHOX2B gene, a key regulator of neural crest cells. Hirschsprung disease is characterized by the congenital absence of neural crest-derived intrinsic ganglion cells. Tonic pupils may result from an abnormality of the ciliary ganglion, another structure of neural crest origin. The close association of these conditions in this child suggests a common abnormality in neural crest migration and differentiation.

AIM To investigate the relationship between neuron density of the superior cervical sympathetic ganglia and pupil diameter in subarachnoid hemorrhage. MATERIAL AND METHODS This study was conducted on 22 rabbits; 5 for the baseline control group, 5 for the SHAM group and 12 for the study group. Pupil diameters were measured via sunlight and ocular tomography on day 1 as the control values. Pupil diameters were re-measured after injecting 0.5 cc saline to the SHAM group, and autologous arterial blood into the cisterna magna of the study group. After 3 weeks, the brain, superior cervical sympathetic ganglia and ciliary ganglia were extracted with peripheral tissues bilaterally and examined histopathologically. Pupil diameters were compared with neuron densities of the sympathetic ganglia and ciliary ganglia which were examined using stereological methods. RESULTS Baseline values were; normal pupil diameter 7.180±620 ?m and mean neuron density of the superior cervical sympathetic ganglia 6.321±510/mm3, degenerated neuron density of ciliary ganglia was 5±2/mm3 after histopathological examination in the control group. These values were measured as 6.850±578 ?m, 5.950±340/mm3 and 123±39/mm3 in the SHAM group and 9.910±840 ?m, 7.950±764/mm3 and 650±98/mm3 in the study group. A linear relationship was determined between neuron density of the superior cervical sympathetic ganglia and pupil diameters (p < 0.005). Degenerated ciliary ganglia neuron density had an inverse effect on pupil diameters in all groups (p < 0.0001). CONCLUSION Highly degenerated neuron density of the ciliary ganglion is not responsible for pupil dilatation owing to parasympathetic pupilloconstrictor palsy, but high neuron density of the pupillodilatatory superior cervical sympathetic ganglia should be considered an important factor for pupil dilatation.

For ophthalmologists, examination of the pupillomotor pathway starts with screening for the conditions of the intraocular segment. Neurologists, during the routine examination of the cranial nerves, regularly use the examination methods of the pupillomotor pathway. In topographical diagnostics, knowing the physiological phenomena and the examination methods is important for both ophthalmologists and neurologists.

The orbitopalpebral region is a complex anatomofunctional unit, formed by several structures to support, protect, and assist the eye in performing the visual function.

Photophobia is defined as a painful psychosomatic discomfort triggered by intense light flow through the pupils to the brain, but the exact mechanism through which photophobia is induced by subarachnoid hemorrhage (SAH) is not well understood. In this study, we aimed to investigate whether there was any relationship between the mydriasis induced by the degeneration of the ciliary ganglion (CG) and photophobia in instances of SAH.Five of a total of 25 rabbits were used as the intact control group; five were used in the sham-operated control group; and the remaining 15 were used as the SAH group, which was created by injecting autologous blood into their cisterna magna. All animals were examined daily for 20days to evaluate their level of photophobia, after which their brains, CGs and superior cervical ganglia (SCGs) were extracted bilaterally. The densities of normal and degenerated neurons in these ganglia were examined by stereological methods.In SAH animals with a high photophobia score, the mean pupil diameter and density of degenerated neurons density in the CG were greater than in cases with a low photophobia score (p0.05). Further analysis revealed that the increase in the density of degenerated neurons in the CG following SAH resulted in the paralysis of the parasympathetic pathway of the pupillary muscles and mydriasis, which facilitates the excessive transfer of light to the brain and photophobia.Our findings indicate that SAH results in a high density of degenerated neurons in the CG, which induces mydriasis and is an important factor in the onset of photophobia. This phenomenon is likely due to more light energy being transferred through mydriatic pupils to the brain, resulting in vasospasm of the supplying arteries.

Examinations of eye movements offer an easy clinical method for the diagnosis of disturbances in the pathways for the generation of eye movements including the extraocular and inner eye muscles. A prerequisite is a good knowledge of the anatomy of the pathways for the generation of eye movements. The oculomotor nucleus represents an important relay station, which contains not only the motoneurons of four extraocular muscles and the levator palpebrae muscle, but also the preganglionic neurons of the ciliary ganglion for the mediation of the pupillary and accommodation response. Recent work about the special anatomy of the extraocular muscles and histochemical findings about the neurons in the Edinger-Westphal nucleus (EW), which indicated that this nucleus does not contain the preganglionic neurons of the ciliary ganglion, led to a new, modified map of the oculomotor nucleus complex. The most serious alteration refers to the location of the preganglionic neurons, which form a group of scattered neurons outside of the EW and now are termed EWpg. In contrast, the traditional cytoarchitectonically defined EW in the human eye contains peptidergic neurons with a completely different function, e.g., stress related, and is therefore termed EWcp (centrally projecting). A knowledge about the exact locations of extraocular motoneurons and preganglionic neurons is essential for the correct interpretation of clinico-anatomic findings.

The cranial parasympathetic ganglia have been reported to paradoxically contain the sympathetic nerve marker, tyrosine hydroxylase (TH), in addition to neurons expressing parasympathetic markers such as vasoactive intestinal peptide (VIP) and neuronal nitric oxide synthase (nNOS). However, the distribution of these molecules in the cranial ganglia of human fetuses has not yet been examined. Using paraffin sections from 10 mid-term human fetuses (12-15 weeks), we performed immunohistochemistry for TH, VIP, and nNOS in the parasympathetic ciliary, pterygopalatine, otic, and submandibular ganglia, and for comparison, the sensory inferior vagal ganglion. The ciliary and submandibular ganglia contained abundant TH-positive neurons. In the former, TH-positive neurons were much more numerous than nNOS-positive neurons, whereas in the latter, nNOS immunoreactivity was extremely strong. No or a few cells in the pterygopalatine, otic, and inferior vagal ganglia expressed TH. Ciliary TH neurons appeared to compensate for classically described sympathetic fibers arising from the superior cervical ganglion, whereas in the submandibular ganglion, nNOS-positive neurons as well as TH neurons might innervate the lingual artery in addition to the salivary glands. Significant individual variations in the density of all these markers suggested differences in sensitivity to medicine affecting autonomic nerve function. Consequently, in the human cranial autonomic ganglia, it appears that there is no simple dichotomy between sympathetic and parasympathetic function.

In this review we summarize current understanding of the development of autonomic neurons in vertebrates. The mechanisms controlling the development of sympathetic and enteric neurons have been studied in considerable detail in laboratory mammals, chick and zebrafish, and there are also limited data about the development of sympathetic and enteric neurons in amphibians. Little is known about the development of parasympathetic neurons apart from the ciliary ganglion in chicks. Although there are considerable gaps in our knowledge, some of the mechanisms controlling sympathetic and enteric neuron development appear to be conserved between mammals, avians and zebrafish. For example, some of the transcriptional regulators involved in the development of sympathetic neurons are conserved between mammals, avians and zebrafish, and the requirement for Ret signalling in the development of enteric neurons is conserved between mammals (including humans), avians and zebrafish. However, there are also differences between species in the migratory pathways followed by sympathetic and enteric neuron precursors and in the requirements for some signalling pathways.

Light intensity is an important determinant of diverse physiological and behavioral responses within the non-image-forming visual system. Thresholds differ among various photic responses, namely control of circadian rhythms, vigilance state, activity level and pupil constriction, but the mechanisms that regulate photosensitivity are not known. Calbindin D(28k) (CalB) is a calcium-binding protein associated with light processing in the mammalian circadian clock. Loss-of-function studies indicate that CalB-deficient mice (CalB(-/-)) have deficits in their ability to entrain to light-dark cycles. To explore the role of CalB in modulating photosensitivity, thresholds for three behaviors mediated by the non-image-forming visual system (entrainment, masking and pupillary light reflex; PLR) were compared in CalB(-/-) and wildtype mice, and the localization of CalB protein in these circuits was examined in adult and juvenile mice. The results reveal a divergence in how CalB affects thresholds to photic cues among these responses. Entrainment and masking were 40- to 60-fold less sensitive in CalB(-/-) than in wildtype mice. On the other hand, the PLR in CalB(-/-) mice was 80- to 200-fold more sensitive. Though CalB is expressed in the retina and in brain circuits regulating entrainment we found no CalB expression in any component of the PLR pathway, namely the olivary pretectal nucleus, Edinger-Westphal nucleus and ciliary ganglion. The behavioral and anatomical data together suggest that, in normal animals, the retinal response to light is blunted in the presence of CalB, but responsiveness of the higher order processes that transduce afferent retinal input is enhanced.

Purpose These experiments were designed to reveal the location of the premotor neurons that have previously been designated physiologically as the midbrain near response cells controlling vergence, lens accommodation, and pupillary constriction in response to target distance. Methods To identify this population, the fixed N2c strain of rabies virus was injected into the ciliary body of seven Macaca fascicularis monkeys. The virus was trans-synaptically transported to the brain. Following a 58- to 76-hour survival, animals were perfused with formalin fixative. After frozen sectioning, tissue was reacted to reveal the location of the infected populations by use of a monoclonal anti-rabies antibody. Another series of sections was processed to determine which of the rabies-positive cells were cholinergic motoneurons by use of an antibody to choline acetyl transferase. Results At earlier time points, only cholinergic cells in the preganglionic Edinger-Westphal nucleus ipsilateral to the injection were labeled. At later time points, an additional population of noncholinergic, premotor cells was present. These were most numerous at the caudal end of the supraoculomotor area, where they formed a bilateral band, oriented mediolaterally immediately above the oculomotor nucleus. Rostral to this, a smaller bilateral population was located near the midline within the supraoculomotor area. Conclusions Most lens preganglionic motoneurons are multipolar cells making up a continuous column within the Edinger-Westphal nucleus. A population of premotor cells that likely represents the midbrain near response cells is located in the supraoculomotor area. These cells are bilaterally distributed relative to the eye they control, and are most numerous caudally.

Somatostatin and cortistatin are neuromodulators with divergent expression patterns and biological roles. Whereas expression and function of genes encoding somatostatin (PSS1) and the related peptide cortistatin (PSS2) have been studied in detail for the central nervous system (CNS) and immune system, relatively little is known about their expression patterns in the peripheral nervous system (PNS). We compare the expression patterns of PSS1 and PSS2 in chicken embryos. At E14, PSS1 is higher in the CNS versus PNS, whereas PSS2 is higher in the PNS. During early development, PSS1 is transiently expressed in lumbar sympathetic ganglia and is detectable at low levels throughout the development of dorsal root and ciliary ganglia. In contrast, PSS2 expression increases as development progresses in sympathetic and dorsal root ganglia, whereas levels in ciliary ganglia by E8 are more than 100-fold higher than in sympathetic ganglia. Activin, which induces somatostatin-like immunoreactivity in ciliary ganglion neurons in vivo and in vitro, controls PSS2 expression by stabilizing PSS2 but not PSS1 mRNA. We conclude that much of the somatostatin-like immunoreactivity in the developing avian peripheral nervous system is actually cortistatin, the PSS2 product, as opposed to true somatostatin, which is the PSS1 product. The identification of PSS2 as the predominantly expressed somatostatin gene family member in avian autonomic neurons provides a molecular basis for further functional and pharmacological studies.

Neuropeptides collaborate with conventional neurotransmitters to regulate synaptic output. Pituitary adenylate cyclase-activating polypeptide (PACAP) co-localizes with acetylcholine in presynaptic nerve terminals, is released by stimulation, and enhances nicotinic acetylcholine receptor- (nAChR-) mediated responses. Such findings implicate PACAP in modulating nicotinic neurotransmission, but relevant synaptic mechanisms have not been explored. We show here that PACAP acts via selective high-affinity G-protein coupled receptors (PAC1Rs) to enhance transmission at nicotinic synapses on parasympathetic ciliary ganglion (CG) neurons by rapidly and persistently increasing the frequency and amplitude of spontaneous, impulse-dependent nicotinic excitatory postsynaptic currents (sEPSCs). Of the canonical adenylate cyclase (AC) and phospholipase-C (PLC) transduction cascades stimulated by PACAP/PAC1R signaling, only AC-generated signals are critical for synaptic modulation since the increases in sEPSC frequency and amplitude were mimicked by 8-Bromo-cAMP, blocked by inhibiting AC or cAMP-dependent protein kinase (PKA), and unaffected by inhibiting PLC. Despite its ability to increase agonist-induced nAChR currents, PACAP failed to influence nAChR-mediated impulse-independent miniature EPSC amplitudes (quantal size). Instead, evoked transmission assays reveal that PACAP/PAC1R signaling increased quantal content, indicating that it modulates synaptic function by increasing vesicular ACh release from presynaptic terminals. Lastly, signals generated by the retrograde messenger, nitric oxide- (NO-) are critical for the synaptic modulation since the PACAP-induced increases in spontaneous EPSC frequency, amplitude and quantal content were mimicked by NO donor and absent after inhibiting NO synthase (NOS). These results indicate that PACAP/PAC1R activation recruits AC-dependent signaling that stimulates NOS to increase NO production and control presynaptic transmitter output at neuronal nicotinic synapses.

Large-conductance Ca2+-activated K+ (BKCa) channels encoded by the Slo1 gene are often components of large multiprotein complexes in excitable and nonexcitable cells. Here we show that Slo1 proteins interact with Neph1, a member of the immunoglobulin superfamily expressed in slit diaphragm domains of podocytes and in vertebrate and invertebrate nervous systems. This interaction was established by reciprocal coimmunoprecipitation of endogenous proteins from differentiated cells of a podocyte cell line, from parasympathetic neurons of the embryonic chick ciliary ganglion, and from HEK293T cells heterologously expressing both proteins. Neph1 can interact with all three extreme COOH-terminal variants of Slo1 (Slo1VEDEC, Slo1QEERL, and Slo1EMVYR) as ascertained by glutathione S-transferase (GST) pull-down assays and by coimmunoprecipitation. Neph1 is partially colocalized in intracellular compartments with endogenous Slo1 in podocytes and ciliary ganglion neurons. Coexpression in HEK293T cells of Neph1 with any of the Slo1 extreme COOH-terminal splice variants suppresses their steady-state expression on the cell surface, as assessed by cell surface biotinylation assays, confocal microscopy, and whole cell recordings. Consistent with this, small interfering RNA (siRNA) knockdown of endogenous Neph1 in embryonic day 10 ciliary ganglion neurons causes an increase in steady-state surface expression of Slo1 and an increase in whole cell Ca2+-dependent K+ current. Surprisingly, a comparable Neph1 knockdown in podocytes causes a decrease in surface expression of Slo1 and a decrease in whole cell BKCa currents. In podocytes, Neph1 siRNA also caused a decrease in nephrin, even though the Neph1 siRNA had no sequence homology with nephrin. However, we could not detect nephrin in ciliary ganglion neurons.

In all vertebrates, including humans, the Edinger-Westphal nucleus (EW) forms a circumscribed cell group dorsomedial to the oculomotor nucleus (nIII). Traditionally the EW is considered the location of parasympathetic preganglionic neurons of the ciliary ganglion, mediating pupillary constriction and accommodation. In a comparative study in rat, ferret, monkey, and human, the location of cholinergic neurons within and around the nIII, which includes motoneurons of the extra-ocular muscles and the preganglionic neurons of the ciliary ganglion, was compared to the location of urocortin-positive neurons. Irrespective of the species, the cholinergic and urocortin-positive neurons form largely separated cell populations adjacent to each other. Only in monkey, cholinergic putative preganglionic neurons were found within the cytoarchitecturally defined EW, whereas in rat, ferret, and human the EW is almost exclusively composed of urocortin-positive neurons. In humans, the presumed preganglionic neurons are located as an inconspicuous group of choline acetyltransferase-positive neurons dorsal to the urocortin-positive EW.

N-cadherin is a transmembrane adhesion receptor that contributes to neuronal development and synapse formation through homophilic interactions that provide structural-adhesive support to contacts between cell membranes. In addition, N-cadherin homotypic binding may initiate cell signaling that regulates neuronal physiology. In this study, we investigated signaling capabilities of N-cadherin that control voltage activated calcium influx. Using whole-cell voltage clamp recording of isolated inward calcium currents in freshly isolated chick ciliary ganglion neurons we show that the juxtamembrane region of N-cadherin cytoplasmic domain regulates high-threshold voltage activated calcium currents by interacting with p120-catenin and activating RhoA. This regulatory mechanism requires myosin interaction with actin. Furthermore, N-cadherin homophilic binding enhanced voltage activated calcium current amplitude in dissociated neurons that have already developed mature synaptic contacts in vivo. The increase in calcium current amplitude was not affected by brefeldin A suggesting that the effect is caused via direct channel modulation and not by increasing channel expression. In contrast, homotypic N-cadherin interaction failed to regulate calcium influx in freshly isolated immature neurons. However, RhoA inhibitors enhanced calcium current amplitude in these immature neurons, suggesting that the inhibitory effect of RhoA on calcium entry is regulated during neuronal development and synapse maturation. These results indicate that N-cadherin modulates voltage activated calcium entry by a mechanism that involves RhoA activity and its downstream effects on the cytoskeleton, and suggest that N-cadherin provides support for synaptic maturation and sustained synaptic activity by facilitating voltage activated calcium influx.

Purpose: To determine pathways of sympathetic nerves from the orbital apex to the eyelids in human cadaver tissue using immunohistochemistry. Methods: Human cadaver orbit tissue was sectioned and immunolabeled with a monoclonal antityrosine hydroxylase antibody. Results: In the orbital apex, the nasociliary, frontal, lacrimal, and maxillary branches of the trigeminal nerve demonstrated intense staining upon entering the orbit. Immunoreactive axons from the nasociliary and frontal nerves were observed to join the extraocular motor nerves in the posterior orbit. A plexus of immunolabeled nerves was observed to accompany the ophthalmic artery as it entered the orbital apex. The ophthalmic artery and its branches throughout the orbit demonstrated staining of nerve fibers in the peripheral muscularis. The nasociliary nerve contributed sympathetic branches to the ciliary ganglion. Nerves passing through the ciliary ganglion and a few ganglion cell bodies demonstrated mild to moderate tyrosine hydroxylase reactivity. Axons within the short and long ciliary nerves demonstrated strong tyrosine hydroxylase reactivity and were observed to enter the posterior sclera and the suprachoroidal space. The lacrimal gland demonstrated mild pericapillary staining and occasional stromal nerve fibers reactive to the antityrosine hydroxylase antibody. Muller muscle and the inferior tarsal muscle possessed a strong tyrosine hydroxylase-reactive nerve supply that appeared to originate from the anterior terminal branches of the nasociliary and lacrimal nerves. Conclusions: Sympathetic nerves enter the orbit via the first and second divisions of the trigeminal nerve and a plexus of nerves surrounding the ophthalmic artery. Extraocular motor nerves receive a sympathetic nerve supply from the sensory nerves in the posterior orbit. Some ciliary ganglion cell bodies demonstrated tyrosine hydroxylase-like reactivity, suggesting a sympathetic modulatory role for the ciliary ganglion. Sympathetics innervate ocular structures via the posterior ciliary nerves. Sympathetic axons travel anteriorly in the orbit via the nasociliary and lacrimal nerves to innervate the sympathetic eyelid muscles. Sympathetic nerves also travel with the frontal branch of the ophthalmic nerve to innervate the forehead skin. The ophthalmic artery and all of its branches contain a perivascular sympathetic nerve supply that may be involved in regulation of blood flow to ocular and orbital structures.

Neuroligin, SynCAM, and L1-CAM are cell adhesion molecules with synaptogenic roles in glutamatergic pathways. We show here that SynCAM is expressed in the chick ciliary ganglion, embedded in a nicotinic pathway, and, as shown previously for neuroligin and L1-CAM, acts transcellularly to promote synaptic maturation on the neurons in culture. Moreover, we show that electroporation of chick embryos with dominant negative constructs disrupting any of the three molecules in vivo reduces the total amount of presynaptic SV2 overlaying the neurons expressing the constructs. Only disruption of L1-CAM and neuroligin, however, reduces the number of SV2 puncta specifically overlaying nicotinic receptor clusters. Disrupting L1-CAM and neuroligin together produces no additional decrement, indicating that they act on the same subset of synapses. SynCAM may affect synaptic maturation rather than synapse formation. The results indicate that individual neurons can express multiple synaptogenic molecules with different effects on the same class of nicotinic synapses.

Muscular dystrophy patients often show cognitive impairment, in addition to muscle degeneration caused by dystrophin gene defects. The cognitive impairments lead to speculation that the dystrophin protein family may play a key role at neuronal synapses. Dystrophin regulates the stability of selected GABA(A) receptor subtypes and alpha3-containing nicotinic acetylcholine receptors (nAChRs) at a subset of central GABAergic and peripheral sympathetic nicotinic neuron synapses. Similarly, utrophin, the autosomal homologue of dystrophin, is not required for clustering but indirectly stabilizes muscle-type nAChRs at the neuromuscular junction. We examined dystrophin and utrophin expression and localization in the avian parasympathetic ciliary ganglion (CG) to determine whether these proteins play a general role at neuronal nicotinic synapses. We have determined that full-length utrophin and dystrophin and the short dystrophin isoform Dp116 are the major isoforms expressed in the CG based on immunoblotting and immunolabeling. Unexpectedly, the cytoskeletal proteins were not detected at nicotinic synapses or in CG neurons. They are expressed in myelinating and non-myelinating Schwann cells. Further, utrophin expression developmentally precedes that of dystrophin. The proteins show partially overlapping distributions, but also differential accumulation along the surface membrane of Schwann cells adjacent to neuronal somata versus axonal processes. Our findings are consistent with reports that dystrophin protein family members function in the maintenance of cell-cell interactions and myelination by anchoring the Schwann cell surface membrane to the basal lamina. In contrast, our results differ from those in skeletal muscle and a subset of sympathetic neurons where utrophin and dystrophin localize at nicotinic synapses.

The ocular motor nerves supply motor fibers to the extraocular muscles of the globe and levator muscle of the eyelid and parasympathetic pupillomotor fibers to the ciliary ganglion. Lesions are classified according to the anatomic location at which they occur: nuclear, fascicular, cisternal, cavernous, or orbital apex. The course each nerve follows influences the sites at which it is most vulnerable to damage and the pathologies to which it is exposed. Cranial nerve palsies frequently are associated with neurologic deficits that may assist in localizing the lesion anatomically. This article provides an overview of the pathology of the ocular motor nerves.

Urocortin is a novel neurotransmitter that appears to play a role in eating and drinking behavior. Most urocortin-positive (urocortin+) neurons in rodents are found in the cytoarchitecturally defined Edinger-Westphal nucleus (EW). However, the EW is traditionally described as the source of the preganglionic parasympathetic outflow to the ciliary ganglion. We examined the distribution of urocortin+ cells and motoneurons by use of immunohistochemical staining for this peptide and for choline acetyltransferase (ChAT) in macaque monkeys, in which most preganglionic motoneurons inhabit the EW, and in cats, in which most do not. In both species, lack of overt double labeling indicated that the ChAT+ and urocortin+ cells are separate populations. In the monkey, most nonoculomotor ChAT+ neurons were found within the EW. In contrast, urocortin+ cells were distributed mainly between the oculomotor nuclei and in the supraoculomotor area. In the cat, most nonoculomotor ChAT+ cells were located in the supraoculomotor area and anteromedian nucleus. Few were present in the cat EW. Instead, this nucleus was filled with urocortin+ cells. These results highlight the fact the term EW has come to indicate different nuclei in different species. Consequently, we have adopted the identifiers preganglionic (EWPG) and urocortin-containing (EWU) to designate the cytoarchitecturally defined EW nuclei in monkeys and cats, respectively. Furthermore, we propose a new open-ended nomenclature for the perioculomotor (pIII) cells groups that have distinctive projections and neurochemical signatures. This will allow more effective scientific discourse on the connections and function of groups such as the periculomotor urocortin (pIIIU) and preganglionic (pIIIPG) populations. J. Comp. Neurol. 507:1300–1316, 2008. © 2008 Wiley-Liss, Inc.

The perioculomotor region contains several functional cell groups, including parasympathetic preganglionic neurons of the ciliary ganglion, motoneurons of multiply innervated muscle fibers (MIF) of extraocular muscles, and urocortin-positive neurons. In this study, midbrain sections of monkey and human were treated with antibodies against choline acetyltransferase (ChAT), cytochrome oxidase (CytOx), nonphosphorylated neurofilaments (NP-NF), chondroitin sulfate proteoglycan (CSPG), and urocortin (UCN) to identify them by their histochemical properties. To facilitate the comparison between species, a new nomenclature was introduced (see also May et al., 2007), which designates these perioculomotor cell populations (pIII) in terms of their function and histochemical properties. The name Edinger-Westphal nucleus (EW) is kept for the cytoarchitecturally defined cell group traditionally considered as the location of preganglionic neurons of the ciliary ganglion. In monkey, the EW contains ChAT-positive presumed preganglionic neurons, and is therefore termed EW(PG), but in contrast human EW consists of noncholinergic UCN-positive neurons, and is therefore termed EW(U). In human, the presumed preganglionic neurons were found dorsal to EW(U), as an inconspicuous group of ChAT- and CytOx-positive neurons. They were interspersed with prominent CSPG-positive cells, a pattern also present in monkey. For the first time, the MIF motoneurons could be identified around the medial aspect of the human oculomotor nucleus as a group of ChAT-positive neurons that lack CSPG-positive perineuronal nets. Moreover, the Perlia nucleus was found to share the histochemical properties of oculomotor twitch motoneurons. The present results form the basis for addressing the appropriate functional cell groups in correlative clinicopathological studies.