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Anja K. E. Horn - One of the best experts on this subject based on the ideXlab platform.
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transmitter inputs to different motoneuron subgroups in the oculomotor and Trochlear Nucleus in monkey
Frontiers in Neuroanatomy, 2015Co-Authors: Christina Zeeh, Michael J Mustari, Bernhard J M Hess, Anja K. E. HornAbstract: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.
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Brainstem cutting planes and transverse sections.
2015Co-Authors: Scott D. Z. Eggers, Anja K. E. Horn, Sigrun Roeber, Wolfgang Härtig, Govind Nair, Daniel S. Reich, John R. LeighAbstract:(A) Brainstem sagittal view demonstrating cutting planes. The blocks containing the rostral interstitial Nucleus of the medial longitudinal fascicle (RIMLF), the oculomotor Nucleus (nIII), the paramedian pontine reticular formation (PPRF) including the excitatory (EBN) and inhibitory burst neurons (IBN), the Nucleus raphe interpositus (RIP) containing omnipause neurons (OPN), and the abducens Nucleus (nVI), were cut in series of 10μm and 5μm thick sections. (B) Caudal view of the block containing the RIMLF. (C) Caudal view of the block containing the PPRF and OPN region. Scale bar B,C = 1cm. INC, interstitial Nucleus of Cajal; IO, inferior olive; MB, mammillary body; LGN, lateral geniculate Nucleus; MCP, medial cerebellar peduncle; MGN, medial geniculate Nucleus; MT, mammillothalamic tract; nIV, Trochlear Nucleus; NVI, abducens nerve; PC, posterior commissure; RN, red Nucleus; TR, tractus retroflexus; PC, posterior commissure; PUL, pulvinar; SC, superior colliculus; SCP, superior cerebellar peduncle; SN, substantia nigra.
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Delineation of motoneuron subgroups supplying individual eye muscles in the human oculomotor Nucleus.
Frontiers in neuroanatomy, 2014Co-Authors: Emmanuel Che Ngwa, Jean A. Büttner-ennever, Christina Zeeh, Ahmed Messoudi, Anja K. E. HornAbstract:The oculomotor Nucleus (nIII) contains the motoneurons of medial, inferior and superior recti (MR, IR, SR), inferior oblique (IO) and levator palpebrae (LP) muscles. The delineation of motoneuron subgroups for each muscle is well-known in monkey, but not in human. We studied the transmitter inputs to human nIII and the Trochlear Nucleus (nIV), which innervates the superior oblique muscle (SO), to outline individual motoneuron subgroups. Parallel series of sections from human brainstems were immunostained for different markers: acetylcholine transferase (ChAT) combined with glutamate decarboxylase (GAD), calretinin (CR) or glycine receptor (GlyR). The cytoarchitecture was visualized with Cresyl violet, Gallyas staining and expression of non-phosphorylated neurofilaments (NP-NF). Apart from nIV, seven subgroups were delineated in nIII: the central caudal Nucleus (CCN), a dorsolateral (DL), dorsomedial (DM), central (CEN), and ventral group (VEN), the Nucleus of Perlia (NP) and the non-preganglionic centrally projecting Edinger-Westphal Nucleus (EWcp). DL, VEN, NP and EWcp were characterized by a strong supply of GAD-positive terminals, in contrast to DM, CEN and nIV. CR-positive terminals and fibres were confined to CCN, CEN and NP. Based on location and histochemistry of the motoneuron subgroups in monkey, CEN is considered as the SR and IO motoneurons, DL and VEN as the B- and A-group of MR motoneurons, respectively, and DM as IR motoneurons. A good correlation between monkey and man is seen for the CR input, which labels only motoneurons of eye muscles participating in upgaze (SR, IO and LP). The CCN contained LP motoneurons, and nIV those of SO. This study provides a map of the individual subgroups of motoneurons in human nIII for the first time, and suggests that NP may contain upgaze motoneurons. Surprisingly, a strong GABAergic input to human MR motoneurons was discovered, which is not seen in monkey and may indicate a functional oculomotor specialization.
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motoneurons of twitch and nontwitch extraocular muscle fibers in the abducens Trochlear and oculomotor nuclei of monkeys
The Journal of Comparative Neurology, 2001Co-Authors: Jean A Buttnerennever, Anja K. E. Horn, Hansjoerg Scherberger, Paola DascanioAbstract:Eye muscle fibers can be divided into two categories: nontwitch, multiply innervated muscle fibers (MIFs), and twitch, singly innervated muscle fibers (SIFs). We investigated the location of motoneurons supplying SIFs and MIFs in the six extraocular muscles of monkeys. Injections of retrograde tracers into eye muscles were placed either centrally, within the central SIF endplate zone; in an intermediate zone, outside the SIF endplate zone, targeting MIF endplates along the length of muscle fiber; or distally, into the myotendinous junction containing palisade endings. Central injections labeled large motoneurons within the abducens, Trochlear or oculomotor Nucleus, and smaller motoneurons lying mainly around the periphery of the motor nuclei. Intermediate injections labeled some large motoneurons within the motor nuclei but also labeled many peripheral motoneurons. Distal injections labeled small and medium-large peripheral neurons strongly and almost exclusively. The peripheral neurons labeled from the lateral rectus muscle surround the medial half of the abducens Nucleus: from superior oblique, they form a cap over the dorsal Trochlear Nucleus; from inferior oblique and superior rectus, they are scattered bilaterally around the midline, between the oculomotor Nucleus; from both medial and inferior rectus, they lie mainly in the C-group, on the dorsomedial border of oculomotor Nucleus. In the medial rectus distal injections, a “C-group extension” extended up to the Edinger-Westphal Nucleus and labeled dendrites within the supraoculomotor area. We conclude that large motoneurons within the motor nuclei innervate twitch fibers, whereas smaller motoneurons around the periphery innervate nontwitch, MIF fibers. The peripheral subgroups also contain medium-large neurons which may be associated with the palisade endings of global MIFs. The role of MIFs in eye movements is unclear, but the concept of a final common pathway must now be recon
Christopher A Salvatore - One of the best experts on this subject based on the ideXlab platform.
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localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem a detailed study using in situ hybridization immunofluorescence and autoradiography
The Journal of Comparative Neurology, 2016Co-Authors: Sajedeh Eftekhari, Renee C Gaspar, Rhonda Roberts, Tsingbau Chen, Zhizhen Zeng, Stephanie Villarreal, Lars Edvinsson, Christopher A SalvatoreAbstract:Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary Nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe Nucleus, gracile Nucleus and spinal trigeminal Nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, Trochlear Nucleus, dorsal raphe Nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens Nucleus, motor trigeminal Nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)
Sajedeh Eftekhari - One of the best experts on this subject based on the ideXlab platform.
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localization of cgrp receptor components and receptor binding sites in rhesus monkey brainstem a detailed study using in situ hybridization immunofluorescence and autoradiography
The Journal of Comparative Neurology, 2016Co-Authors: Sajedeh Eftekhari, Renee C Gaspar, Rhonda Roberts, Tsingbau Chen, Zhizhen Zeng, Stephanie Villarreal, Lars Edvinsson, Christopher A SalvatoreAbstract:Functional imaging studies have revealed that certain brainstem areas are activated during migraine attacks. The neuropeptide calcitonin gene-related peptide (CGRP) is associated with activation of the trigeminovascular system, transmission of nociceptive information and plays a key role in migraine pathophysiology. Therefore, to elucidate the role of CGRP it is critical to identify the regions within the brainstem that processes CGRP signaling. In situ hybridization and immunofluorescence were performed to detect mRNA expression and define cellular localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1), respectively. To define CGRP receptor binding sites, in vitro autoradiography was performed with [(3) H]MK-3207 (a CGRP receptor antagonist). CLR and RAMP1 mRNA and protein expression were detected in the pineal gland, medial mammillary Nucleus, median eminence, infundibular stem, periaqueductal gray, area postrema, pontine raphe Nucleus, gracile Nucleus and spinal trigeminal Nucleus and the spinal cord. RAMP1 mRNA expression was also detected in the posterior hypothalamic area, Trochlear Nucleus, dorsal raphe Nucleus, medial lemniscus, pontine nuclei, vagus nerve, inferior olive, abducens Nucleus, motor trigeminal Nucleus; where protein co-expression of CLR and RAMP1 was observed via immunofluorescence. [(3) H]MK-3207 showed high binding densities concordant with mRNA and protein expression. The present study suggests that several regions in the brainstem may be involved in CGRP signaling. Interestingly, we found receptor expression and antagonist binding in some areas that are not protected by the blood-brain barrier, which suggests that CGRP receptor antagonists may not need to be CNS-penetrant to antagonize receptors in these brain regions. This article is protected by copyright. All rights reserved. (Less)
Christina Zeeh - One of the best experts on this subject based on the ideXlab platform.
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transmitter inputs to different motoneuron subgroups in the oculomotor and Trochlear Nucleus in monkey
Frontiers in Neuroanatomy, 2015Co-Authors: Christina Zeeh, Michael J Mustari, Bernhard J M Hess, Anja K. E. HornAbstract: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.
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Delineation of motoneuron subgroups supplying individual eye muscles in the human oculomotor Nucleus.
Frontiers in neuroanatomy, 2014Co-Authors: Emmanuel Che Ngwa, Jean A. Büttner-ennever, Christina Zeeh, Ahmed Messoudi, Anja K. E. HornAbstract:The oculomotor Nucleus (nIII) contains the motoneurons of medial, inferior and superior recti (MR, IR, SR), inferior oblique (IO) and levator palpebrae (LP) muscles. The delineation of motoneuron subgroups for each muscle is well-known in monkey, but not in human. We studied the transmitter inputs to human nIII and the Trochlear Nucleus (nIV), which innervates the superior oblique muscle (SO), to outline individual motoneuron subgroups. Parallel series of sections from human brainstems were immunostained for different markers: acetylcholine transferase (ChAT) combined with glutamate decarboxylase (GAD), calretinin (CR) or glycine receptor (GlyR). The cytoarchitecture was visualized with Cresyl violet, Gallyas staining and expression of non-phosphorylated neurofilaments (NP-NF). Apart from nIV, seven subgroups were delineated in nIII: the central caudal Nucleus (CCN), a dorsolateral (DL), dorsomedial (DM), central (CEN), and ventral group (VEN), the Nucleus of Perlia (NP) and the non-preganglionic centrally projecting Edinger-Westphal Nucleus (EWcp). DL, VEN, NP and EWcp were characterized by a strong supply of GAD-positive terminals, in contrast to DM, CEN and nIV. CR-positive terminals and fibres were confined to CCN, CEN and NP. Based on location and histochemistry of the motoneuron subgroups in monkey, CEN is considered as the SR and IO motoneurons, DL and VEN as the B- and A-group of MR motoneurons, respectively, and DM as IR motoneurons. A good correlation between monkey and man is seen for the CR input, which labels only motoneurons of eye muscles participating in upgaze (SR, IO and LP). The CCN contained LP motoneurons, and nIV those of SO. This study provides a map of the individual subgroups of motoneurons in human nIII for the first time, and suggests that NP may contain upgaze motoneurons. Surprisingly, a strong GABAergic input to human MR motoneurons was discovered, which is not seen in monkey and may indicate a functional oculomotor specialization.
Marco R Celio - One of the best experts on this subject based on the ideXlab platform.
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efferent connections of the parvalbumin positive pv1 Nucleus in the lateral hypothalamus of rodents
The Journal of Comparative Neurology, 2013Co-Authors: Marco R Celio, Alexandre Babalian, Quan Hue Ha, Simone Eichenberger, Laurence Clement, Christiane Marti, Clifford B SaperAbstract:A solitary cluster of parvalbumin-positive neurons – the PV1 Nucleus – has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 Nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 Nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor Nucleus (Su3). It is spatially interrupted over a short stretch at the level of the Trochlear Nucleus and abuts caudally on a second parvalbumin-positive (PV2) Nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 Nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger–Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 Nucleus. J. Comp. Neurol. 521:3133–3153, 2013. © 2013 Wiley Periodicals, Inc.
