Oculomotor Nucleus Research Articles

Extraocular motoneuron pools develop along a dorsoventral axis in zebrafish, Danio rerio.

ABSTRACTBoth spatial and temporal cues determine the fate of immature neurons. A major challenge at the interface of developmental and systems neuroscience is to relate this spatiotemporal trajectory of maturation to circuit‐level functional organization. This study examined the development of two extraocular motor nuclei (nIII and nIV), structures in which a motoneuron's identity, or choice of muscle partner, defines its behavioral role. We used retro‐orbital dye fills, in combination with fluorescent markers for motoneuron location and birthdate, to probe spatial and temporal organization of the oculomotor (nIII) and trochlear (nIV) nuclei in the larval zebrafish. We describe a dorsoventral organization of the four nIII motoneuron pools, in which inferior and medial rectus motoneurons occupy dorsal nIII, while inferior oblique and superior rectus motoneurons occupy distinct divisions of ventral nIII. Dorsal nIII motoneurons are, moreover, born before motoneurons of ventral nIII and nIV. The order of neurogenesis can therefore account for the dorsoventral organization of nIII and may play a primary role in determining motoneuron identity. We propose that the temporal development of extraocular motoneurons plays a key role in assembling a functional oculomotor circuit. J. Comp. Neurol. 525:65–78, 2017. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Differential neuronal vulnerability identifies IGF-2 as a protective factor in ALS.

The fatal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons leading to muscle wasting and paralysis. However, motor neurons in the oculomotor nucleus, controlling eye movement, are for unknown reasons spared. We found that insulin-like growth factor 2 (IGF-2) was maintained in oculomotor neurons in ALS and thus could play a role in oculomotor resistance in this disease. We also showed that IGF-1 receptor (IGF-1R), which mediates survival pathways upon IGF binding, was highly expressed in oculomotor neurons and on extraocular muscle endplate. The addition of IGF-2 induced Akt phosphorylation, glycogen synthase kinase-3β phosphorylation and β-catenin levels while protecting ALS patient motor neurons. IGF-2 also rescued motor neurons derived from spinal muscular atrophy (SMA) patients from degeneration. Finally, AAV9::IGF-2 delivery to muscles of SOD1G93A ALS mice extended life-span by 10%, while preserving motor neurons and inducing motor axon regeneration. Thus, our studies demonstrate that oculomotor-specific expression can be utilized to identify candidates that protect vulnerable motor neurons from degeneration.

Krüpple-like factors 7 and 6a mRNA expression in adult zebrafish central nervous system

Krüpple-like factors (KLFs) are transcription factors with zinc finger DNA binding domains known to play important roles in brain development and central nervous system (CNS) regeneration. There is little information on KLFs expression in adult vertebrate CNS. In this study, we used in situ hybridization to examine Klf7 mRNA (klf7) and Klf6a mRNA (klf6a) expression in adult zebrafish CNS. Both klfs exhibit wide and similar expression in the zebrafish CNS. Brain areas containing strongly labeled cells include the ventricular regions of the dorsomedial telencephalon, the ventromedial telencephalon, periventricular regions of the thalamus and hypothalamus, torus longitudinalis, stratum periventriculare of the optic tectum, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. In the spinal cord, klf7- and klf6a-expressing cells are found in both the dorsal and ventral horns. Numerous sensory structures (e.g. auditory, lateral line, olfactory and visual) and several motor nuclei (e.g. oculomotor, trigeminal, and vagal motor nuclei) contain klf7- and/or klf6a-expressing cells. Our results may provide useful information for determining these Klfs in maintenance and/or function in adult CNS.

Correlation of tau pathology in eye movement related brainstem nuclei in cases of progressive supranuclear palsy (PSP) and a proposed role of perineuronal nets

Background Progressive supranuclear palsy (PSP) is characterized by hyperphosphorylated tau protein (HTP) accumulations in different brain regions. A hallmark of clinical symptoms is a vertical gaze palsy, which may be accompanied by horizontal gaze palsy, whereas the VOR is rather preserved until late in the disease. Based on monkey studies functional cell groups of the oculomotor system including transmitters have been identified in the human brainstem (Buttner-Ennever & Horn, 2010). Methods To study the spread of the disease through the oculomotor premotor network sections of 8 archival PSP cases with different eye movement deficits were immunostained for HTP. The analysis involved the glutaminergic rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF) and paramedian pontine reticular formation (PPRF), the glycinergic saccadic omnipause neurons (OPN), the cholinergic oculomotor nucleus (nIII) and the vestibular nuclei (VN). Since the RIMLF and nIII contain well-developed perineuronal nets (PN) (Horn et al., 2003), we further stained sections of the PSP cases for the presence of aggrecan (ACAN) and HTP to prove a possible protective role of PNs as suggested from Alzheimer's disease cases (Morawski et al., 2010). Results All PSP-cases showed HTP-staining in neurons and glia of RIMLF, PPRF and OPNs, in late cases in motonuclei as well. Thereby a correlation between eye movement deficits and degeneration of premotor gaze centers and the complete pathways to motoneurons was found, whereas the VN are less affected. The analysis of PNs revealed that ACAN-based PNs were mainly found around HTP-negative neurons, and only few HTP-positive neurons showed weak ACAN staining. Conclusions The early and more severe degeneration of premotor centers compared to nIII support a hypothesis that in PSP the pathology progresses along neuronal chains in an anterograde fashion, and it is not confined to specific transmitters. The severe tau pathology in RIMLF and nIII in late PSP cases implies that the presence of PNs may not protect them from degeneration, but on a cellular basis the integrity of PNs is affected by tau-pathology. Support: BMBF (IFB-01EO0901, Brain-Net-01GI0505).

Ultrastructure of Motoneurons and Synapses in the Nuclei of the Oculomotor Nerves in Mice

The ultrastructure of motoneurons and synapses in the somatic zone of the oculomotor nerve nuclei was studied in C57 Black/6 mice. Axodendritic and axosomatic synapses were characterized by round densities (round subjunctional densities) located in the postsynaptic part of the synapse some distance from the postsynaptic density. The synaptic cleft close to subjunctional densities was widened to up to 30 μm. Other parts of the cleft in the same synapse could be narrowed almost twofold. Axosomatic and axodendritic spiny synapses were found. Motoneuron bodies and dendrites bore synapses of the en passant type. Gap junctions were not seen.

Deficits in the Activation of Human Oculomotor Nuclei in Chronic Traumatic Brain Injury.

Binocular eye movements form a finely tuned system that requires accurate coordination of the oculomotor dynamics of the brainstem control nuclei when tracking the fine binocular disparities required for 3D vision. They are particularly susceptible to disruption by brain injury and other neural dysfunctions. Here, we report functional magnetic resonance imaging activation of the brainstem oculomotor control nuclei by binocular saccadic and vergence eye movements, and significant reductions in their response amplitudes in mild or diffuse traumatic brain injury (dTBI). Bilateral signals were recorded from a non-TBI control group (n = 11) in the oculomotor control system of the superior colliculi, the oculomotor nuclei, the abducens nuclei, and in the supra-oculomotor area (SOA), which mediate vergence eye movements. Signals from these nuclei were significantly reduced overall in a dTBI group (n = 12) and in particular for the SOA for vergence movements, which also showed significant decreases in velocity for both the convergence and divergence directions.

Vestibular-evoked myogenic potentials in central vestibular disorders.

Vestibular-evoked myogenic potentials (VEMPs) are short latency manifestations of vestibulo-ocular and vestibulocollic reflexes that originate from the utricle and saccule. Although cervical and ocular VEMPs have mostly been applied to peripheral vestibular disorders, the characteristics and the diagnostic values of VEMPs have been expanded to assess the function of the central otolithic pathways. In the central nervous system, the cervical VEMPs (cVEMPs) are mediated by the vestibular nuclei and uncrossed medial vestibulospinal tract descending in the lower brainstem and spinal cord. In contrast, the ocular VEMPs (oVEMPs) reflect the function of the vestibular nuclei and the crossed vestibulo-ocular reflex (VOR) pathways, mostly contained in the medial longitudinal fasciculus (MLF). Therefore, lesions involving the vestibular nuclei can present abnormalities of both cVEMPs and oVEMPs. The medullary lesions involving the descending MLF or the spinal accessory nucleus impair cVEMPs. In contrast, the lesions involving the MLF, the crossed ventral tegmental tract, oculomotor nuclei and the interstitial nucleus of Cajal can impair oVEMPs. Patients with unilateral cerebellar infarctions may show abnormal VEMPs especially when they have the ocular tilt reaction. Delayed responses of VEMPs are characteristic of multiple sclerosis (MS). Reduced VEMP responses can be observed in patients with vestibular migraine. VEMPs are useful in evaluating central as well as peripheral otolithic function that are not readily defined by conventional vestibular function tests, and can aid in detecting and localizing central lesions, especially silent brainstem lesions such as tiny infarctions or MS plaques.

The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice

Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3.

Commentary on “Monosodium glutamate neurotoxicity increases beta amyloid in the rat hippocampus: A potential role for cyclic AMP protein kinase” ( )

Methylmercury (MeHg) is a widely distributed environmental neurotoxin with established effects on locomotor behaviors and cognition in both human populations and animal models. Despite well-described neurobehavioral effects, the mechanisms of MeHg toxicity are not completely understood. Previous research supports a role for oxidative stress in the toxic effects of MeHg. However, comparing findings across studies has been challenging due to differences in species, methodologies (in vivo or in vitro studies), dosing regimens (acute vs. long-term) and developmental life stage. The current studies assess the behavioral effects of MeHg in adult mice in conjunction with biochemical and cellular indicators of oxidative stress using a consistent dosing regimen. In Experiment 1, adult male C57/BL6 mice were orally administered 5 mg/kg/day MeHg or the vehicle for 28 days. Impact of MeHg exposure was assessed on inverted screen and Rotor-Rod behaviors as well as on biomarkers of oxidative stress (thioredoxin reductase (TrxR), glutathione reductase (GR) and glutathione peroxidase (GPx)) in brain and liver. In Experiment 2, brain tissue was immunohistochemically labeled for 8-hydroxy-2′-deoxyguanosine (8-OHdG), a biomarker of DNA oxidation and an indicator of oxidative stress, following the same dosing regimen. 8-OHdG immunoreactivity was measured in the motor cortex, the magnocellular red nucleus (RMC) and the accessory oculomotor nucleus (MA3). Significant impairments were observed in MeHg-treated animals on locomotor behaviors. TrxR and GPx was significantly inhibited in brain and liver, whereas GR activity decreased in liver and increased in brain tissue of MeHg-treated animals. Significant MeHg-induced alterations in DNA oxidation were observed in the motor cortex, the RMC and the MA3.

A central mesencephalic reticular formation projection to the supraoculomotor area in macaque monkeys.

The central mesencephalic reticular formation is physiologically implicated in oculomotor function and anatomically interwoven with many parts of the oculomotor system's premotor circuitry. This study in Macaca fascicularis monkeys investigates the pattern of central mesencephalic reticular formation projections to the area in and around the extraocular motor nuclei, with special emphasis on the supraoculomotor area. It also examines the location of the cells responsible for this projection. Injections of biotinylated dextran amine were stereotaxically placed within the central mesencephalic reticular formation to anterogradely label axons and terminals. These revealed bilateral terminal fields in the supraoculomotor area. In addition, dense terminations were found in both the preganglionic Edinger-Westphal nuclei. The dense terminations just dorsal to the oculomotor nucleus overlap with the location of the C-group medial rectus motoneurons projecting to multiply innervated muscle fibers suggesting they may be targeted. Minor terminal fields were observed bilaterally within the borders of the oculomotor and abducens nuclei. Injections including the supraoculomotor area and oculomotor nucleus retrogradely labeled a tight band of neurons crossing the central third of the central mesencephalic reticular formation at all rostrocaudal levels, indicating a subregion of the nucleus provides this projection. Thus, these experiments reveal that a subregion of the central mesencephalic reticular formation may directly project to motoneurons in the oculomotor and abducens nuclei, as well as to preganglionic neurons controlling the tone of intraocular muscles. This pattern of projections suggests an as yet undetermined role in regulating the near triad.

Internal organization of medial rectus and inferior rectus muscle neurons in the C group of the oculomotor nucleus in monkey.

Mammalian extraocular muscles contain singly innervated twitch muscle fibers (SIF) and multiply innervated nontwitch muscle fibers (MIF). In monkey, MIF motoneurons lie around the periphery of oculomotor nuclei and have premotor inputs different from those of the motoneurons inside the nuclei. The most prominent MIF motoneuron group is the C group, which innervates the medial rectus (MR) and inferior rectus (IR) muscle. To explore the organization of both cell groups within the C group, we performed small injections of choleratoxin subunit B into the myotendinous junction of MR or IR in monkeys. In three animals the IR and MR myotendinous junction of one eye was injected simultaneously with different tracers (choleratoxin subunit B and wheat germ agglutinin). This revealed that both muscles were supplied by two different, nonoverlapping populations in the C group. The IR neurons lie adjacent to the dorsomedial border of the oculomotor nucleus, whereas MR neurons are located farther medially. A striking feature was the differing pattern of dendrite distribution of both cell groups. Whereas the dendrites of IR neurons spread into the supraoculomotor area bilaterally, those of the MR neurons were restricted to the ipsilateral side and sent a focused bundle dorsally to the preganglionic neurons of the Edinger-Westphal nucleus, which are involved in the "near response." In conclusion, MR and IR are innervated by independent neuron populations from the C group. Their dendritic branching pattern within the supraoculomotor area indicates a participation in the near response providing vergence but also reflects their differing functional roles.

Motor neurons with differential vulnerability to degeneration show distinct protein signatures in health and ALS

The lethal disease amyotrophic lateral sclerosis (ALS) is characterized by the loss of somatic motor neurons. However, not all motor neurons are equally vulnerable to disease; certain groups are spared, including those in the oculomotor nucleus controlling eye movement. The reasons for this differential vulnerability remain unknown. Here we have identified a protein signature for resistant oculomotor motor neurons and vulnerable hypoglossal and spinal motor neurons in mouse and man and in health and ALS with the aim of understanding motor neuron resistance. Several proteins with implications for motor neuron resistance, including GABAA receptor α1, guanylate cyclase soluble subunit alpha-3 and parvalbumin were persistently expressed in oculomotor neurons in man and mouse. Vulnerable motor neurons displayed higher protein levels of dynein, peripherin and GABAA receptor α2, which play roles in retrograde transport and excitability, respectively. These were dynamically regulated during disease and thus could place motor neurons at an increased risk. From our analysis is it evident that oculomotor motor neurons have a distinct protein signature compared to vulnerable motor neurons in brain stem and spinal cord, which could in part explain their resistance to degeneration in ALS. Our comparison of human and mouse shows the relative conservation of signals across species and infers that transgenic SOD1G93A mice could be used to predict mechanisms of neuronal vulnerability in man.

The nucleus prepositus hypoglossi contributes to head direction cell stability in rats.

Head direction (HD) cells in the rat limbic system fire according to the animal's orientation independently of the animal's environmental location or behavior. These HD cells receive strong inputs from the vestibular system, among other areas, as evidenced by disruption of their directional firing after lesions or inactivation of vestibular inputs. Two brainstem nuclei, the supragenual nucleus (SGN) and nucleus prepositus hypoglossi (NPH), are known to project to the HD network and are thought to be possible relays of vestibular information. Previous work has shown that lesioning the SGN leads to a loss of spatial tuning in downstream HD cells, but the NPH has historically been defined as an oculomotor nuclei and therefore its role in contributing to the HD signal is less clear. Here, we investigated this role by recording HD cells in the anterior thalamus after either neurotoxic or electrolytic lesions of the NPH. There was a total loss of direction-specific firing in anterodorsal thalamus cells in animals with complete NPH lesions. However, many cells were identified that fired in bursts unrelated to the animals' directional heading and were similar to cells seen in previous studies that damaged vestibular-associated areas. Some animals with significant but incomplete lesions of the NPH had HD cells that were stable under normal conditions, but were unstable under conditions designed to minimize the use of external cues. These results support the hypothesis that the NPH, beyond its traditional oculomotor function, plays a critical role in conveying vestibular-related information to the HD circuit.

Distribution of choline acetyltransferase (ChAT) immunoreactivity in the CNS of the common carp Cyprinus carpio

Cholinergic systems play a role in basic cerebral functions and a number of human neurodegenerative disorders. Mechanisms involved in human brain diseases, including Parkinson’s disease (1), are often approached by using fish models, especially cyprinids, given basic similarities of the fish brain to that of mammals. In the present paper, the organization of central cholinergic systems have been described in the cyprinid Cyprinus carpio , the common carp, by using specific polyclonal antibodies against ChAT, the synthetic enzyme of acetylcholine, that is currently used as a specific marker for cholinergic neurons in all vertebrates. In this work, serial transverse and sagittal sections of the brain and the spinal cord were immunostained for ChAT. Results showed that positive neurons are present in several nuclei. In particular, ChAT-immunoreactive (ir) neurons were found in the forebrain (preoptic region, habenula), the midbrain (optic tectum, oculomotor nucleus, rostral tegmental nucleus), the hindbrain and the spinal cord (reticular formation, nucleus isthmi, secundary gustatory nucleus, cranial nerve motor nuclei from IV to X, spinal cord motoneurons). Moreover, ChAT-ir neurons were detected in the synencephalon (nucleus of the medial longitudinal fascicle) and in the cerebellum. In addition to neuronal bodies, afferent varicose fibers were stained for ChAT in the ventral telencephalon, the preoptic area, the hypothalamus and the posterior tuberculum. No neuronal cell bodies were present in the telencephalon. The comparison of ChAT-ir distribution observed in the present study with that reported in other CNS of cyprinids (2,3) has revealed a number of similarities and also some interesting differences. Our results provide additional information on the cholinergic system from a phylogenetic point of view, suggesting that cholinergic systems of the common carp show many primitive features that have been conserved during evolution, together with characteristics that are exclusive. In addition, the present study may add new perspectives to physiological roles of cholinergic system during evolution and the neuroanatomical basis of neurological diseases.

Transmitter inputs to different motoneuron subgroups in the oculomotor and trochlear nucleus in monkey.

In all vertebrates the eyes are moved by six pairs of extraocular muscles enabling horizontal, vertical and rotatory movements. Recent work showed that each extraocular muscle is controlled by two motoneuronal groups: (1) Motoneurons of singly-innervated muscle fibers (SIF) that lie within the boundaries of motonuclei mediating a fast muscle contraction; and (2) motoneurons of multiply-innervated muscle fibers (MIF) in the periphery of motonuclei mediating a tonic muscle contraction. Currently only limited data about the transmitter inputs to the SIF and MIF motoneurons are available. Here we performed a quantitative study on the transmitter inputs to SIF and MIF motoneurons of individual muscles in the oculomotor and trochlear nucleus in monkey. Pre-labeled motoneurons were immunostained for GABA, glutamate decarboxylase, GABA-A receptor, glycine transporter 2, glycine receptor 1, and vesicular glutamate transporters 1 and 2. The main findings were: (1) the inhibitory control of SIF motoneurons for horizontal and vertical eye movements differs. Unlike in previous primate studies a considerable GABAergic input was found to all SIF motoneuronal groups, whereas a glycinergic input was confined to motoneurons of the medial rectus (MR) muscle mediating horizontal eye movements and to those of the levator palpebrae (LP) muscle elevating the upper eyelid. Whereas SIF and MIF motoneurons of individual eye muscles do not differ numerically in their GABAergic, glycinergic and vGlut2 input, vGlut1 containing terminals densely covered the supraoculomotor area (SOA) targeting MR MIF motoneurons. It is reasonable to assume that the vGlut1 input affects the near response system in the SOA, which houses the preganglionic neurons mediating pupillary constriction and accommodation and the MR MIF motoneurones involved in vergence.

Top of Basilar Artery Syndrome.

A 45 years old male presented in Department of Medicine at the Shree Shayaji General Hospital with sudden onset bilateral ptosis, dilatation of the pupil and paresis of extraocular muscles. There were area of restricted diffusion on diffusion weighted images with corresponding low ADC (Apparent Diffusion Coefficient) value in periaqueductal region, oculomotor nucleus and medial thalami suggestive of acute infract. In MR cerebral angiographic image filling defect is seen in the basilar artery suggestive of thrombosis [Table/Fig-1,​,22,​,3].3]. Top of the Basilar Artery Syndrome is also known as a Rostral Brainstem Infarction. It is due to the thromboembolic occlusion of the top of the basilar artery. Risk factors for the thrombosis are hypertension [1], diabetes mellitus [2], obesity [2], hyperhomocystinemia [3], and excessive alcohol intake. It may be secondary to the cardiogenic emboli like mural thrombi in myocardial infarction and atrial fibrillations or valvular thrombi in infective endocarditic and valvular heart disease. Hypercoaguable states like antiphospholipid antibodies [4], protein C deficiency [4], protein S deficiency [4] may also leads to the thrombotic events. Small vessel vaculities in sickle cell disease may be associated with it. Bilateral tha lamic ischemia occurs due to occlusion of perforator vessels. Clinically patient develops symptoms like visual and oculomotor deficits and behavioral abnormalities. However, motor dysfunction is often absent [5]. CT angiography, MR angiography and catheter angiographic are the imaging modality use to confirm the finding and demonstrate a filling defect [6]. Prognosis in patient with bilateral ocular palsy is poor. [Table/Fig-1a,b]: Axial section of diffusion weighted MR image shows (A) area of restricted diffusion in oculomotor nuclei region in midbrain (open white arrow) (B) area of restricted diffusion in bilateral medial thalami (open white arrow) [Table/Fig-2a,b]: Axial section of Apparent Diffusion map shows (A) corresponding low ADC value in oculomotor nuclei region in medulla (black solid arrow) (B) in bilateral medial thalami (solid white arrow) [Table/Fig-3a,b]: MR angiographic images shows filling defect in the basilar artery suggestive of thrombosis Top of the basilar artery syndrome is occurring due to thrombotic occlusion of the basilar artery. Patient presented with visual and oculomotor deficit and behaviour abnormalities. MR angiography demonstrate filling defect in the basilar artery.

Monocular Diplopia Associated with a Midbrain Stroke

Background and Purpose Monocular diplopia is often due to intraocular disease. It is rarely the result of cerebral causes, which include lesions in or near Brodmann’s area nineteen, the frontal eye fields or the cerebellum. Monocular diplopia has not been reported in a patient with a midbrain lesion. Methods and Results A patient with a history of hypertension presented with right monocular diplopia and headache. There was no ocular cause of the patient’s symptoms, and aside from bilateral ptosis, there were no relevant findings on neurological examination. MRI brain revealed an ischemic stroke affecting the right oculomotor nucleus. Her evaluation, including an ECG and 48-hour Holter monitor was unremarkable. A subsequent 30-day auto-trigger cardiac event monitor revealed paroxysmal atrial fibrillation. Conclusions This case shows that monocular diplopia can be associated with a midbrain lesion and underscores the importance of prolonged cardiac monitoring in patients with otherwise cryptogenic stroke.

Is hyperexcitability really guilty in amyotrophic lateral sclerosis?

Amyotrophic lateral sclerosis (ALS) is a lethal disorder characterized by the gradual degeneration of brainstem and spinal motoneurons as well as lateral cortico-spinal tracts. The onset generally occurs during the adult age except for some juvenile aggressive forms. Until recently, the vast majority of the cases (90%) were deemed sporadic. Mutations in the SOD1 gene have been for a long time the only ones reported in familiar forms of ALS. However, the recent implication of new genes of little known function cast a new view on this disease. C9ORF72, for example, is now recognized to account for 30% of the familial cases. Overall, ALS has been linked to 20 different genes, many also associated with other degenerative diseases (frontotemporal dementia, Alzheimer or ataxia). Some of these genes are involved in RNA maturation (FUS, TARBD). Clinical observation of human patients and mouse models suggests that all motor pools and motoneurons are not equally affected (see Kanning et al., 2010). The disease usually starts in motor pools controlling the limbs or in the bulbar area before expanding to other motor pools, with the exception of a few resistant ones (Onuf's and oculomotor nuclei). Within a vulnerable motor pool, motoneurons subtypes also exhibit differential vulnerability and follow an orderly degeneration; starting with the motoneurons innervating fast-contracting fatigable motor units (FF motoneurons) and followed by the ones innervating fast-contractile fatigue-resistant motor units (FR motoneurons). The motoneurons innervating slow motor units (S motoneurons) appear resistant to the disease. Although the mechanisms leading to the orderly degeneration are not known, many hypotheses have been raised (Ilieva et al., 2009).

Isolated nuclear III nerve paresis secondary to neurocysticercosis showing spontaneous clinical improvement.

Sir, We wish to present a case of isolated nuclear IIIrd nerve paresis secondary to neurocysticercosis (NCC) showing spontaneous clinical improvement. Isolated third cranial nerve palsy is rare in NCC. A 14-year-old male child of Nepali origin presented with diplopia for 6 days in left lateral gaze and drooping of his upper eyelids in both eyes. The complaints were insidious in onset, non-progressive simultaneous in both eyes with no diurnal fluctuation. Rest of his present and past medical history was not significant. He had history of pork consumption. His general physical examination and systemic examination including neurological examination was unremarkable. His visual acuity was 6/6 OU with increased wrinkling on forehead. He had severe neurological ptosis in both eyes with poor levator palpebrae superioris (LPS) action with no Marcus Gunn phenomenon and no sign s/o fatigueability. He also had an exotropia of about 15 degree and mild paresis of elevation of eyeball in right eye maximum in lateral gaze. He had mild paresis of his right medial rectus with end gaze nystagmus in left gaze. Rest of the ophthalmological examination was unremarkable including papillary reactions. Diplopia charting showed horizontal diplopia in all gaze positions with maximum difference in left lateral gaze positions [Figure 1]. While waiting for his investigation reports his sign and symptoms showed spontaneous clinical improvement. His magnetic resonance imaging (MRI) showed a solitary ring-enhancing lesion in the pre-aqueductal region of mid brain of size 0.72 × 0.68 cm involving IIIrd nerve nucleus with peri lesional edema [Figure 2]. His lumbar puncture was done and it revealed CSF protein levels 60 and it also showed 9 white blood cells mainly lymphocytes. ADA levels in his CSF were within normal limit. His serology revealed positive IgG levels for taenia solium (1.13 U/ml) by ELISA. In the light of the above findings the patient was diagnosed as a case of nuclear third nerve paresis secondary to NCC of brainstem. After consultation with Department of Neurology the patient was put on oral albendazole and prednisolone. He was continuously followed up with no similar episodes till 1 year after. Figure 1 (a) Ptosis in both eyes. (b) Paresis of Medial rectus in right eye. (c) Paresis of elevation in right eye. (d-f) Respective improvement Figure 2 Transverse section in MRI showing solitary ring enhancing lesion in the pre-aqueductal region of mid brain of size 0.72 × 0.68 cm involving IIIrd nerve nucleus with peri lesional edema NCC is the most common parasitic infestation of the nervous system.[1] Globally, NCC is endemic in Central and South America, sub-Saharan Africa, and in some regions of the Far East, including the Indian subcontinent, Indonesia, and China, reaching an incidence of 3.6% in some regions.[1] Del Brutto et al. have suggested diagnostic criteria for NCC.[2] In our case these criteria were fulfilled for probable diagnosis of NCC. It usually presents with seizures. Other various CNS clinical manifestations include headache, hydrocephalus, chronic meningitis, focal neurological deficits, dementia and psychiatric manifestations.[3] Involvement of third nerve is rare especially due to a parenchymal lesion.[4] Fluctuation in perilesional edema was probably responsible for spontaneous clinical recovery in our patient. The lesion in such nuclear third nerve paresis involves the central caudal nucleus (CCN), which is a small subgroup of oculomotor nucleus containing subnucleus for levator palpebrae superioris.[5] Involvement of this nucleus results in complete, bilateral ptosis. We propose a more detailed evaluation of patients with fluctuating ptosis. In those patients where ptosis is restricted to ocular muscle without any other neuromuscular involvement, cranial imaging needs to be done, preferably MRI of the brain with contrast studies that may show lesions in the midbrain.

Distribution of the vasotocin type 4 receptor throughout the brain of the chicken, Gallus gallus.

The vasopressin 1a receptor (V1aR) has been shown to have a wide distribution throughout the mammalian brain and pituitary gland and mediates a number of physiological functions as well as social behavior following the binding of its agonist, vasopressin. The avian receptor homologous to the V1aR is the vasotocin 4 receptor (VT4R). Its mRNA distribution has been documented in brain regions of two species of songbird; however, its complete protein distribution in the brain has not been published to date for any avian species. The present work utilizes an antibody made to a sequence of the chicken VT4R to map its distribution from the olfactory bulbs to the caudal end of the brainstem in Gallus gallus. Unexpectedly, immunoreactivity (ir) for the VT4R was found not only in neurons but also in glia located in 10 circumventricular organs (CVOs), olfactory bulbs, hippocampus, and septum. Use of a second antibody made against vimentin provided evidence that some dual-labeled glial cells were tanycytes and radial glia. Additionally, the VT4R was identified in nuclei related to motor function, including the oculomotor complex and motor nucleus of the fourth, fifth, sixth, seventh, tenth, and twelfth cranial nerves. Possible functions for the VT4R are suggested that should have relevance not only to avian species but to other vertebrates because most classes, except for mammals, use vasotocin as the natural ligand for that receptor.