Cranial Nerve Motor Nuclei Research Articles

Brainstem Surgery: Functional Surgical Anatomy with the Use of an Advanced Modern Intraoperative Neurophysiological Procedure.

Intraoperative neurophysiology (ION) in brainstem surgery evolved as brainstem surgery advanced.The original idea of brainstem mapping (BSM) is a neurophysiological procedure to locate cranial nerve motor nuclei (CNMN) on the floor of the fourth ventricle. With the introduction of various skull base approaches to the brainstem, BSM is carried out on any surface of the brainstem to expose the safe entry zone to the intrinsic brainstem lesion. It is the modern concept of BSM, a broader definition of BSM. BSM enables to avoid direct damage to the CNMN when approaching the brainstem through the negative mapping region.The corticobulbar tract (CBT) motor evoked potential (MEP) is another ION procedure in brainstem surgery. It enables monitoring of the functional integrity of the whole cranial motor pathway without interrupting surgical procedures. Combined application of both BSM and CBT-MEP monitoring is indispensable for the functional preservation of the CNMN and their supranuclear innervation during the brainstem surgery.In this paper, the neurophysiological aspect of BSM and the CBT-MEP was fully described. Normal anatomical background of the floor of the fourth ventricle and the detail of the CBT anatomy were demonstrated to better understand their clinical usefulness, limitations, and surgical implications derived from ION procedures. Finally, a future perspective in the role of ION procedures in brainstem surgery was presented. The latest magnetic resonance imaging (MRI) technology can allow surgeons to find an "on the image" safe entry zone to the brainstem. However, the role of BSM and the CBT-MEP monitoring in terms of safe brainstem surgery stays unshakable. Special attention was paid for the recent trend of management in diffuse intrinsic pontine gliomas. A new role of BSM during a stereotactic biopsy was discussed.It is the authors' expectation that the paper enhances the clinical application of a contemporary standard of the ION in brainstem surgery and supports safer brainstem surgery more than ever and in the future.

Mapping of STB/HAP1 Immunoreactivity in the Mouse Brainstem and its Relationships with Choline Acetyltransferase, with Special Emphasis on Cranial Nerve Motor and Preganglionic Autonomic Nuclei

Huntingtin-associated protein 1 (HAP1) is a core component of stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for various neurodegenerative diseases. Brain regions rich in STB/HAP1 immunoreactivity are usually spared from cell death, whereas brain regions with negligible STB/HAP1 immunoreactivity are the major neurodegenerative targets. Recently, we have shown that STB/HAP1 is abundantly expressed in the spinal preganglionic sympathetic/parasympathetic neurons but absent in the motoneurons of spinal cord, indicating that spinal motoneurons are more vulnerable to neurodegenerative diseases. In light of STB/HAP1 neuroprotective effects, it is also essential to clarify the distribution of STB/HAP1 in another major neurodegenerative target, the brainstem. Here, we examined the expression and detailed immunohistochemical distribution of STB/HAP1 and its relationships with choline acetyltransferase (ChAT) in the midbrain, pons, and medulla oblongata of adult mice. Abundant STB/HAP1 immunoreactive neurons were disseminated in the periaqueductal gray, Edinger-Westphal nucleus, raphe nuclei, locus coeruleus, pedunculopontine tegmental nucleus, superior/inferior salivatory nucleus, and dorsal motor nucleus of vagus. Double-label immunohistochemistry of HAP1 with ChAT (or with urocortin-1 for Edinger-Westphal nucleus centrally projecting population) confirmed that STB/HAP1 was highly present in parasympathetic preganglionic neurons but utterly absent in cranial nerve motor nuclei throughout the brainstem. These results suggest that due to deficient putative STB/HAP1-protectivity, cranial nerve motor nuclei might be more vulnerable to certain neurodegenerative stresses than STB/HAP1-expressing brainstem nuclei, including preganglionic parasympathetic nuclei. Our current results also lay a basic foundation for future studies that seek to clarify the physiological/pathological roles of STB/HAP1 in the brainstem.

Neuromeric Distribution of Nicotinamide Adenine Dinucleotide Phosphate-Diaphorase Activity in the Adult Lamprey Brain.

This study reports for the first time the distribution and morphological characterization of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d; a reliable marker of nitric oxide synthase activity) positive elements in the central nervous system of the adult river lamprey (Lampetra fluviatilis) on the framework of the neuromeric model and compares their cytoarchitectonic organization with that of gnathostomes. Both NADPH-d exhibiting cells and fibers were observed in all major divisions of the lamprey brain as well as in the spinal cord. In the secondary prosencephalon, NADPH-d positive cells were observed in the mitral cell layer of the olfactory bulb, evaginated pallium, amygdala, dorsal striatum, septum, lateral preoptic nucleus, caudal paraventricular area, posterior entopeduncular nucleus, nucleus of the stria medullaris, hypothalamic periventricular organ and mamillary region sensu lato. In the lamprey diencephalon, NADPH-d labeled cells were observed in several nuclei of the prethalamus, epithalamus, pretectum, and the basal plate. Especially remarkable was the staining observed in the right habenula and several pretectal nuclei. NADPH-d positive cells were also observed in the following mesencephalic areas: optic tectum (two populations), torus semicircularis, nucleus M5 of Schöber, and a ventral tegmental periventricular nucleus. Five different cell populations were observed in the isthmic region, whereas the large sensory dorsal cells, some cells located in the interpeduncular nucleus, the motor nuclei of most cranial nerves, the solitary tract nucleus, some cells of the reticular nuclei, and small cerebrospinal fluid-contacting (CSF-c) cells were the most evident stained cells of the rhombencephalon proper. Finally, several NADPH-d positive cells were observed in the rostral part of the spinal cord, including the large sensory dorsal cells, numerous CSF-c cells, and some dorsal and lateral interneurons. NADPH-d positive fibers were observed in the olfactory pathways (primary olfactory fibers and stria medullaris), the fasciculus retroflexus, and the dorsal column tract. Our results on the distribution of NADPH-d positive elements in the brain of the adult lamprey L. fluviatilis are significantly different from those previously reported in larval lampreys and demonstrated that these animals possess a complex nitrergic system readily comparable to those of other vertebrates, although important specific differences also exist.

Subdivisions of the mesencephalon and isthmus in the lizard Gekko gecko as revealed by ChAT immunohistochemistry.

The distribution of cholinergic cell bodies and fibers was examined in the mesencephalon and isthmus of Gekko gecko. Distinct groups with prominent labeled cells were observed in the cranial nerve motor nuclei and isthmic nuclei, and weak labeled cell bodies and fibers were observed in the mesencephalic nucleus of the trigeminal nerve and the central nucleus of the torus semicircularis. After discussing the topological relationships within the tectum and isthmus, we unify the nomenclature of the caudal deep mesencephalic nucleus in lizards and the rostral magnocellular nucleus isthmi in turtles that is similar in terms of the preisthmic position, nontopographic connections with the tectum, and the same midbrain origin to the magnocellular preisthmic nucleus in birds, and may be homologous to the superficial cuneiform nucleus in mammals. None of them belong to the cholinergic nucleus isthmi, as the latter has isthmus origin and topographic reciprocal connections with the tectum. We also discuss the origin and intrinsic function of the inner longitudinal tract of the thick ChAT-ir fibers that course through the mesencephalon and diencephalon. We review the subdivisions of the mesencephalon and isthmus of Gekko gecko as revealed by ChAT immunohistochemistry, as well as the limits of the diencephalo-mesencephalic, mesencephalic-isthmo, and isthmo-rhombocephalic by the ChAT-ir cell- and fiber-poor distribution, and discuss the caudal limit of the isthmus. Our research on the subdivisions of the mesencephalon and isthmus in G. gecko as revealed by ChAT immunohistochemistry will serve as the neuroanatomical basis for subsequent relevant studies of Gekko gecko.

Facial Nerve Translocation for Low Tension Neurorrhaphy to Masseteric Nerve.

The techniques of facial reanimation are continually evolving in search of the ideal method for rehabilitating the paralyzed face. In the past, alternative cranial nerve motor nuclei have been used to power facial musculature. The trigeminal nerve is gaining popularity as a promising nerve to drive facial motion, particularly in the lower face. This article describes a low-tension technique of using the transposed facial nerve to the trigeminal nerve (masseteric branch) for facial reanimation. Six patients over 2.5 years were treated with facial nerve translocation with division at the geniculate and direct neurorrhaphy to the motor branch of the masseter. Patients were evaluated by physical examination, measurement of oral commissure excursion using MEEI FACE-gram software, video assessment, Sunnybrook Facial Grading System, Facial Disability Index, and Facial Clinimetric Evaluation Scale (FaCE). Patients demonstrated early motion within 4 months postoperatively and were placed into facial physical therapy. All demonstrated improvements in oral competence, strong oral commissure excursion with good symmetry, speech improvements, and variable results in facial tone. Synkinesis to the smile antagonists in the lower face was noted and treated with chemodenervation in three of six. No upper division synkinesis was noted. The motor branch of the trigeminal nerve is an effective option for facial reanimation via facial nerve translocation and end-to-end neurorrhaphy. Variable results in facial tone were noted with excellent oral commissure excursion. This procedure is safe in the reoperated mastoid.

Expression of the transcription factor FOXP2 in brainstem respiratory circuits of adult rat is restricted to upper-airway pre-motor areas

Expression of the transcription factor FOXP2 is linked to brain circuits that control motor function and speech. Investigation of FOXP2 protein expression in respiratory areas of the ponto-medullary brainstem of adult rat revealed distinct rostro-caudal expression gradients. A high density of FOXP2 immunoreactive nuclei was observed within the rostral pontine Kölliker-Fuse nucleus, compared to low densities in caudal pontine and rostral medullary respiratory nuclei, including the: (i) noradrenergic A5 and parafacial respiratory groups; (ii) Bötzinger and pre-Bötzinger complex and; (iii) rostral ventral respiratory group. Moderate densities of FOXP2 immunoreactive nuclei were observed in the caudal ventral respiratory group and the nucleus retroambiguus, with significant density levels found in the caudal half of the dorsal respiratory group and the hypoglossal pre-motor area lateral around calamus scriptorius. FOXP2 immunoreactivity was absent in all cranial nerve motor nuclei. We conclude that FOXP2 expression in respiratory brainstem areas selectively delineates laryngeal and hypoglossal pre-motor neuron populations essential for the generation of sound and voice.

Transfer of pathogenic and nonpathogenic cytosolic proteins between spinal cord motor neurons in vivo in chimeric mice

Recent studies have reported spread of pathogenic proteins in the mammalian nervous system, but whether nonpathogenic ones spread is unknown. We initially investigated whether spread of a mutant amyotrophic lateral sclerosis-associated cytosolic superoxide dismutase 1 (SOD1) protein between motor neurons could be detected in intact chimeric mice. Eight-cell embryos from G85R SOD1YFP and G85R SOD1CFP mice were aggregated, and spinal cords of adult chimeric progeny were examined for motor neurons with cytosolic double fluorescence. By 3 mo of age, we observed extensive double fluorescence, including in amyotrophic lateral sclerosis-affected cranial nerve motor nuclei but not in the relatively spared extraocular nuclei. Chimeras of nonpathogenic wtSOD1YFP and G85R SOD1CFP also exhibited double fluorescence. In a third chimera, mitochondrial mCherry did not transfer to G85R SOD1YFP motor neurons, suggesting that neither RNA nor organelles transfer, but mito-mCherry neurons received G85R SOD1YFP. In a chimera of ChAT promoter-EGFP and mito-mCherry, EGFP efficiently transferred to mito-mCherry+ cells. Thus, nonpathogenic cytosolic proteins appear capable of transfer. During study of both the SOD1FP and EGFP chimeras, we observed fluorescence also in small cells neighboring the motor neurons, identified as mature gray matter oligodendrocytes. Double fluorescence in the G85R SOD1FP chimera and observation of the temporal development of fluorescence first in motor neurons and then in these oligodendrocytes suggest that they may be mediators of transfer of cytosolic proteins between motor neurons.

Localization of glutamatergic, GABAergic, and cholinergic neurons in the brain of the African cichlid fish, Astatotilapia burtoni.

Neural communication depends on release and reception of different neurotransmitters within complex circuits that ultimately mediate basic biological functions. We mapped the distribution of glutamatergic, GABAergic, and cholinergic neurons in the brain of the African cichlid fish Astatotilapia burtoni using in situ hybridization to label vesicular glutamate transporters (vglut1, vglut2.1, vglut3), glutamate decarboxylases (gad1, gad2), and choline acetyltransferase (chat). Cells expressing the glutamatergic markers vgluts 1-3 show primarily nonoverlapping distribution patterns, with the most widespread expression observed for vglut2.1, and more restricted expression of vglut1 and vglut3. vglut1 is prominent in granular layers of the cerebellum, habenula, preglomerular nuclei, and several other diencephalic, mesencephalic, and rhombencephalic regions. vglut2.1 is widely expressed in many nuclei from the olfactory bulbs to the hindbrain, while vglut3 is restricted to the hypothalamus and hindbrain. GABAergic cells show largely overlapping gad1 and gad2 expression in most brain regions. GABAergic expression dominates nuclei of the subpallial ventral telencephalon, while glutamatergic expression dominates nuclei of the pallial dorsal telencephalon. chat-expressing cells are prominent in motor cranial nerve nuclei, and some scattered cells lie in the preoptic area and ventral part of the ventral telencephalon. A localization summary of these markers within regions of the conserved social decision-making network reveals a predominance of either GABAergic or glutamatergic cells within individual nuclei. The neurotransmitter distributions described here in the brain of a single fish species provide an important resource for identification of brain nuclei in other fishes, as well as future comparative studies on circuit organization and function. J. Comp. Neurol. 525:610-638, 2017. © 2016 Wiley Periodicals, Inc.

31. Intraoperative monitoring of motor cranial nerves and cranial nerve nuclei

Intraoperative neurophysiologic monitoring of cranial nerve function is primarily performed in those cranial nerves whose function has a motor component. The rationale, as well as the stimulation and recording techniques employed, is similar to that used in assessing the functional integrity of motor peripheral nerves. The primary difference is in the placement of the recording electrodes and the neural structures that are at risk for injury. In addition, cranial nerve dysfunction is not solely confined to a cranial nerve but can also involve the nucleus of the specific nerve. Thus, a special application of cranial nerve monitoring is the functional assessment and monitoring of cranial nerve nuclei. The goal of this presentation is to review the neurophysiologic techniques, consisting primarily of EMG, used to monitor motor cranial nerves and cranial nerve nuclei, and highlight this with case examples.

Cranial Nerves: Functional Anatomy

This book is pocket-sized, with a soft but sturdy cover and clearly identified titles on the front cover and spine. The inside cover contains a description of the book, highlighting the functional approach to the contents. There are five parts covering organisation of individual cranial nerves and four functionally based topics focusing on the role of cranial nerves during the passage of food through the head and neck. The author has made it clear that the drive for the book is on the clinically useful rather than academic completeness. A note to the reader warns that previous knowledge is needed and also targets undergraduate students in dentistry, medicine and speech therapy, while offering support for postgraduate physicians and healthcare practitioners interested in head and neck medicine. Part I describes the organisation of cranial nerves. The style of the text is conversational, which helps to remove the daunting formality usually associated with the topic. Essential definitions are addressed before explaining cranial nerve motor and sensory nuclei, tracts and brain stem relationships. The style is relaxed, so much so that for the first time this reviewer has encountered the term ‘etc’ used in an anatomical text! Figures add supporting information for the more difficult concepts, focusing on the schematic in favour of the anatomically accurate. Overall, the aims are achieved and the reader advances onto the next parts with a sound basis. Part II commences with a general description of cranial nerves, designed around their role in key functions involved in the eating and swallowing of food. Starting with cutaneous sensation and chewing, the text describes the Vth, VIIth and XIIth cranial nerves. While the detail is broad, the depth does at times fall short of that expected in the more specialist practices such as dentistry and head and neck surgery. Issues such as the sensory nerves involved in supplying maxillary teeth, description of the muscles of mastication and the area of tongue sensation detected by trigeminal nerve branches are the most notable omissions. The facial and hypoglossal nerves are covered accurately and succinctly but surgeons with an interest in parotid gland surgery will be surprised to hear that facial nerve injuries incurred during surgery rarely recover! Part III deals mainly with swallowing and speech, focusing on the role of the IXth, Xth and XIth cranial nerves. The topics covered are wide, informative and well written but the depth at times does fall short of the level expected in most postgraduate specialist examinations. Part IV deals with taste and smell, with very good illustrations of the parasympathetic pathways in the head and neck. The sympathetic system is also well described but suffers from the lack of a suitable illustration. Part V finishes the book by looking at vision and balance. The intricacies of various reflexes are very well covered and the supporting diagrams are an essential adjunct. The role of the IIIrd, IVth and VIth cranial nerves in extra-ocular function is not covered although the various reflexes of the pupil are worthy entries. Balance and hearing, a traditionally complicated topic, is well addressed and presented in an understandable fashion. Each chapter finishes by giving excellent examples of the clinical impact of some of the nerves covered at each stage. This is valuable for the newer student and those still confused by the impact of the information provided. The reading lists provided are reasonable but it does seem strange that no mention is made of Last's Anatomy, which has provided the bulk of the information in the field to the majority of those entering a surgical career. So to whom would this book appeal? For the candidate revising for examinations who had reached a point where larger texts had lost their appeal, this text would allow for a review of facts fast fading and serve to refocus the mind on the important issues. However, the reader would need to be aware that of necessity for a book of this size the depth falls short in some crucial areas. For this reason, it could not be a first choice for those beginning their studies, as candidates may find themselves short of the required knowledge level, especially dental students. Its content and size does make it a worthy companion for preexamination revision but the warning that some prior knowledge is a benefit is something of which the reader should take note.

Generation of a Nkx2.2Cre knock-in mouse line: Analysis of cell lineages in the central nervous system

A Nkx2.2cre knock-in mutant mouse line was generated that on the appropriate reporter strain enables cell fate analysis of the Nkx2.2 cell lineage in the central nervous system and elsewhere. We here demonstrate that Nkx2.2 lineage-marked cells reside in the ventral p3 region along the entire length of the CNS and also in pancreas of mouse embryos. Nkx2.2+ progenitor cells develop into V3 interneurons in spinal cord and generate the branchio-visceral motor nuclei of cranial nerves in hindbrain. Nkx2.2+ cells in hindbrain also form serotonergic neurons and oligodendrocytes during later developmental stages. In mouse mutants lacking Nkx2.2 protein the neuronal progenitor cells in spinal cord are transformed to the distinct fate of somatic motor neurons including their axonal projections that exit the CNS ventrally and no longer cross the midline at the commissure. These data identify Nkx2.2 as key regulator to determine neuronal subtypes in the p3 domain of the central nervous system.

Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity

ABSTRACTCreatine is a molecule that supports energy metabolism in cells. It is carried across the plasma membrane by the creatine transporter. There has been recent interest in creatine for its neuroprotective effects in neurodegenerative diseases and its potential as a therapeutic agent. This study represents the first systematic investigation of the distribution of the creatine transporter in the human brain. We have used immunohistochemical techniques to map out its location and the intensity of staining. The transporter was found to be strongly expressed, especially in the large projection neurons of the brain and spinal cord. These include the pyramidal neurons in the cerebral cortex, Purkinje cells in the cerebellar cortex, and motor neurons of the somatic motor and visceromotor cranial nerve nuclei and the ventral horn of the spinal cord. Many other neurons in the brain also had some degree of creatine transporter immunoreactivity. By contrast, the medium spiny neurons of the striatum and the catecholaminergic neurons of the substantia nigra and locus coeruleus, which are implicated in neurodegenerative diseases, showed a very low to almost absent level of immunoreactivity for the transporter. We propose that the distribution may reflect the energy consumption by different cell types and that the extent of creatine transporter expression is proportional to the cell's energy requirements. Furthermore, the distribution indicates that supplemented creatine would be widely taken up by brain cells, although possibly less by those cells that degenerate in Huntington's and Parkinson's diseases. J. Comp. Neurol. 523:699–725, 2015. © 2014 Wiley Periodicals, Inc.

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.

Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity.

Creatine is a molecule that supports energy metabolism in cells. It is carried across the plasma membrane by the creatine transporter. There has been recent interest in creatine for its neuroprotective effects in neurodegenerative diseases and its potential as a therapeutic agent. This study represents the first systematic investigation of the distribution of the creatine transporter in the human brain. We have used immunohistochemical techniques to map out its location and the intensity of staining. The transporter was found to be strongly expressed, especially in the large projection neurons of the brain and spinal cord. These include the pyramidal neurons in the cerebral cortex, Purkinje cells in the cerebellar cortex, and motor neurons of the somatic motor and visceromotor cranial nerve nuclei and the ventral horn of the spinal cord. Many other neurons in the brain also had some degree of creatine transporter immunoreactivity. By contrast, the medium spiny neurons of the striatum and the catecholaminergic neurons of the substantia nigra and locus coeruleus, which are implicated in neurodegenerative diseases, showed a very low to almost absent level of immunoreactivity for the transporter. We propose that the distribution may reflect the energy consumption by different cell types and that the extent of creatine transporter expression is proportional to the cell's energy requirements. Furthermore, the distribution indicates that supplemented creatine would be widely taken up by brain cells, although possibly less by those cells that degenerate in Huntington's and Parkinson's diseases.

Adrenoreceptor modulation of oromotor pathways in the rat medulla.

Regulation of feeding behavior involves the integration of multiple physiological and neurological pathways that control both nutrient-seeking and consummatory behaviors. The consummatory phase of ingestion includes stereotyped oromotor movements of the tongue and jaw that are controlled through brain stem pathways. These pathways encompass not only cranial nerve sensory and motor nuclei for processing feeding-related afferent signals and supplying the oromotor musculature but also reticular neurons for orchestrating ingestion and coordinating it with other behaviors that utilize the same musculature. Based on decerebrate studies, this circuit should be sensitive to satiety mechanisms mediated centrally by A2 noradrenergic neurons in the caudal nucleus of the solitary tract (cNST) that are potently activated during satiety. Because the first observable phase of satiety is inhibition of oromotor movements, we hypothesized that norepinephrine (NE) would act to inhibit prehypoglossal neurons in the medullary reticular formation. Using patch-clamp electrophysiology of retrogradely labeled prehypoglossal neurons and calcium imaging to test this hypothesis, we demonstrate that norepinephrine can influence both pre- and postsynaptic properties of reticular neurons through both α1- and α2-adrenoreceptors. The α1-adrenoreceptor agonist phenylephrine (PE) activated an inward current in the presence of TTX and increased the frequency of both inhibitory and excitatory miniature postsynaptic currents. The α2-adrenoreceptor agonist dexmedetomidine (DMT) inhibited cNST-evoked excitatory currents as well as spontaneous and miniature excitatory currents through presynaptic mechanisms. The diversity of adrenoreceptor modulation of these prehypoglossal neurons may reflect their role in a multifunctional circuit coordinating both ingestive and respiratory lingual function.

Stages of pTDP‐43 pathology in amyotrophic lateral sclerosis

To see whether the distribution patterns of phosphorylated 43kDa TAR DNA-binding protein (pTDP-43) intraneuronal inclusions in amyotrophic lateral sclerosis (ALS) permit recognition of neuropathological stages. pTDP-43 immunohistochemistry was performed on 70 μm sections from ALS autopsy cases (N = 76) classified by clinical phenotype and genetic background. ALS cases with the lowest burden of pTDP-43 pathology were characterized by lesions in the agranular motor cortex, brainstem motor nuclei of cranial nerves V, VII, and X-XII, and spinal cord α-motoneurons (stage 1). Increasing burdens of pathology showed involvement of the prefrontal neocortex (middle frontal gyrus), brainstem reticular formation, precerebellar nuclei, and the red nucleus (stage 2). In stage 3, pTDP-43 pathology involved the prefrontal (gyrus rectus and orbital gyri) and then postcentral neocortex and striatum. Cases with the greatest burden of pTDP-43 lesions showed pTDP-43 inclusions in anteromedial portions of the temporal lobe, including the hippocampus (stage 4). At all stages, these lesions were accompanied by pTDP-43 oligodendroglial aggregates. Ten cases with C9orf72 repeat expansion displayed the same sequential spreading pattern as nonexpansion cases but a greater regional burden of lesions, indicating a more fulminant dissemination of pTDP-43 pathology. pTDP-43 pathology in ALS possibly disseminates in a sequential pattern that permits recognition of 4 neuropathological stages consistent with the hypothesis that pTDP-43 pathology is propagated along axonal pathways. Moreover, the finding that pTDP-43 pathology develops in the prefrontal cortex as part of an ongoing disease process could account for the development of executive cognitive deficits in ALS.

Comparative Analysis of the Organization of the Cholinergic System in the Brains of Two Holostean Fishes, the Florida Gar Lepisosteus platyrhincus and the Bowfin Amia calva

The cholinergic system in the brain has been widely studied in most vertebrate groups, but there is no information available about this neurotransmission system in the brains of holostean fishes, a primitive and poorly understood group of actinopterygian fishes. The present study provides the first detailed information on the distribution of cholinergic cell bodies and fibers in the central nervous system in two holostean species, the Florida gar, Lepisosteus platyrhincus, and the bowfin, Amia calva. Immmunohistochemistry against the enzyme choline acetyltransferase (ChAT) revealed distinct groups of ChAT-immunoreactive (ChAT-ir) cells in the habenula, isthmic nucleus, laterodorsal tegmental nucleus, octavolateral area, reticular formation, cranial nerve motor nuclei and the motor column of the spinal cord, all of which seem to be highly conserved among vertebrates. Some ChAT-ir cells were detected in the basal telencephalon that appear in actinopterygians for the first time in the evolution of this neurotransmission system, whereas the remarkable cholinergic population in the optic tectum is a peculiar characteristic, the presence of which varies throughout evolution, although it is present in all teleosts studied. Abundant cholinergic fibers were found in the pretectal region and optic tectum, where they probably modulate vision, and in the hypothalamus and the interpeduncular neuropil. Some interspecific differences were also observed, such as the presence of ChAT-ir cells in the supraoptoparaventricular band only in Lepisosteus and in in the nucleus subglomerulosus only in Amia. In addition, ChAT-ir fibers in the olfactory bulb were detected only in Amia. Comparison of these results with those from other classes of vertebrates, and a segmental analysis to correlate cell populations, reveal that the pattern of the cholinergic system in holosteans is very close to that in ancestral actinopterygian fishes, as recently described in the bichir (Cladistia), although an important evolutionary novelty in holosteans is the presence of cholinergic cells in the basal telencephalon.

Pattern of tau hyperphosphorylation and neurotransmitter markers in the brainstem of senescent tau filament forming transgenic mice

The early occurrence of brainstem-related symptoms, e.g. gait and balance impairment, apathy and depression in Alzheimer’s disease patients suggests brainstem involvement in the initial pathogenesis. To address the question whether tau filament forming mice expressing mutated human tau mirror histopathological changes observed in Alzheimer brainstem, the degree and distribution of neurofibrillary lesions as well as the pattern of cholinergic and monoaminergic neurons were investigated. The expression of the human tau transgene was observed in multiple brainstem nuclei, particularly in the magnocellular reticular formation, vestibular nuclei, cranial nerve motor nuclei, sensory trigeminal nerve nuclei, inferior and superior colliculi, periaqueductal and pontine gray matter, and the red nucleus. Most of the human tau-immunoreactive cell groups also showed tau hyperphosphorylation at the epitopes Thr231/Ser235 and Ser202/Thr205, while abnormal tau phosphorylation at the epitope Ser422 or silver stained structures were almost totally lacking. We found no obvious differences in distribution and density of cholinergic and monoaminergic neurons between tau-transgenic and wild type mice. Although numerous brainstem nuclei in our model expressed human tau protein, the development of neurofibrillary tangles, neuropil threads and ghost tangles was rare and likewise its distribution differed largely from Alzheimer′s disease pattern. The number of monoaminergic neurons remained unchanged in the transgenic mice, while monoaminergic nuclei in Alzheimer brainstem showed a distinct neuronal loss. However, the distribution of pretangle-affected neurons in the tau-transgenic mice partly resembled those seen in progressive supranuclear palsy, presenting these animals as a model to examine brainstem pathogenesis of progressive supranuclear palsy.

Osteocalcin- and osteopontin-containing neurons in the rat hind brain.

Immunohistochemistry for osteocalcin (OC) and osteopontin (OPN) was performed to know their distributions in the hind brain of adult rats. OC- and OPN-immunoreactivity (-ir) were detected in neuronal cell bodies, including perikarya and proximal dendrites and the neuropil. In the cranial nerve motor nuclei, numerous OC- and OPN-immunoreactive (-ir) neurons were detected. The neuropil in the cranial motor nuclei mostly showed strong OC- and OPN-staining intensity. The cranial nerve sensory nuclei and other relay and modulating structures in the lower brain stem also contained various numbers of OC- and OPN-ir neurons. The staining intensities in the neuropil were varied among these regions. In the cerebellar cortex, Purkinje cells and granule cells showed OPN-ir but not OC-ir. However, OC- and OPN-ir neurons were abundantly distributed throughout the cerebellar nuclei. The neuropil in the cerebellar nuclei showed moderate OC-ir and strong OPN-ir staining intensities. These findings indicate that the distribution patterns of OC- and OPN-ir neurons were similar in many structures within the hind brain. OC may play a role in modulating neuroprotective function of OPN.

Regional and subcellular distribution of the receptor‐targeting protein PIST in the rat central nervous system

Protein interacting specifically with Tc10, PIST, is a Golgi-associated sorting protein involved in regulating cell-surface targeting of plasma membrane receptors. The present study provides the first comprehensive description of PIST distribution in the mammalian central nervous system and of its subcellular localization by immunocytochemistry. PIST is distributed widely throughout the neuraxis, predominantly associated with neuronal cell bodies and dendrites. In hippocampal neurons, in vitro and in situ, PIST displayed a patchy subcellular distribution in an area surrounding the nucleus and extending into one of the major dendrites. By colocalization with the trans-Golgi marker TGN38, we were able to show that PIST is associated largely but not exclusively with the trans-Golgi network in central neurons. High or moderate to high levels of PIST-like immunoreactivity were found in cortical areas, in particular in layer V of the neocortex. The motor cortex was most strongly labeled. Also, the piriform and insular cortices displayed strong PIST labeling. In the hippocampus, CA2 but not CA1 or CA3 pyramidal cells displayed strong PIST-labeling, extending into their apical dendrites. In the thalamus, ventrolateral and laterodorsal nuclei were most strongly stained, whereas in the hypothalamus the supraoptic nucleus stood out with strong immunoreactivity. Strikingly, in the brainstem all cranial nerve motor nuclei were PIST-positive at varying levels, which is in keeping with the prominent expression of PIST in forebrain motor areas. This selective distribution of PIST suggests that the protein serves distinctive roles in specific neuronal populations, establishing functionally distinct zones, for instance, in the hippocampus.