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

Zeeh, Christina; Mustari, Michael J.; Hess, Bernhard; Horn, Anja K. E.

doi:10.3389/fnana.2015.00095

Cited by 11 publications

(12 citation statements)

References 107 publications

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“…Interestingly, slopes of horizontal and upward saccades, calculated as peak duration (amplitude/PV) vs. amplitude were not significantly associated with any of the clinical measures, perhaps because of both a ceiling level of horizontal saccades reflecting advanced disease and upward saccades being relatively spared by the disease process. The latter is probably caused by calretinin-positive input from premotor centers, interstitial nucleus of Cajal (INC), riMLF, and y-group in upgaze, but not in downgaze pathways ( 19 – 21 ). Calretinin is a calcium-binding protein, and in combination with parvalbumin and perineuronal nets can help identify and analyze the upgaze vs. downgaze ocular motor disturbances in other lysosomal diseases, such as Niemann–Pick disease type C ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

et al. 2018

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Objectives: To evaluate the function of the oculomotor and vestibular systems and to correlate these findings with the clinical status of patients with Gaucher disease type 3 (GD3). The goal of this cross-sectional and longitudinal study was to find oculomotor biomarkers for future clinical trials.Methods: Twenty-six patients with GD3 were assessed for eligibility and 21 were able to perform at least one task. Horizontal and vertical reflexive saccades, smooth pursuit, gaze-holding, optokinetic nystagmus, and horizontal vestibulo-ocular reflex (VOR) were examined by video-oculography/video-head impulse test and compared concurrently with 33 healthy controls. The Scale for the Assessment and Rating of Ataxia (SARA), the modified Severity Scoring Tool (mSST), and Grooved Pegboard Test (GPT) were administered to assess overall neurological function. Eleven patients were also re-assessed after 1 year.results: Nine out of 17 patients exhibited gaze-holding deficits. One patient had upbeat nystagmus. Three patients presented with bilateral abducens palsy in combination with central oculomotor disorders, suggesting a bilateral involvement of the abducens nucleus. Horizontal angular VOR gain was reduced in all patients (0.66 ± 0.37) compared with controls (1.1 ± 0.11, p < 0.001). Most strongly correlated with clinical rating scales were peak velocity of downward saccades (SARA: ρ = −0.752, p < 0.0005; mSST: ρ = −0.611, p = 0.003; GPT: ρ = −0.649, p = 0.005) and duration of vertical saccades interpretation: This study shows neuronal degeneration of the brainstem and cerebellum with combined involvement of both supranuclear and nuclear oculomotor structures and the vestibular system in GD3. We also identified oculomotor parameters that correlate with the neurological status and can be used as biomarkers in future clinical trials.

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Section: Discussionmentioning

confidence: 99%

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

et al. 2018

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“…Calretinin does not serve as a suitable marker for INTs in primates, since our previous work revealed that in rhesus monkey calretinin-positive neurons are not present within the nVI proper (McCrea and Horn, 2006 ). Calretinin was rather found associated with premotor pathways targeting motoneurons involved in upgaze (Horn et al, 2003 ; Ahlfeld et al, 2011 ; Adamczyk et al, 2015 ; Zeeh et al, 2015 ). With 38% the size of the putative INT population within the nVI in human is larger compared to that found in rhesus monkey (26.4%), which may indicate a more elaborate system in human.…”

Section: Discussionmentioning

confidence: 99%

“…Based on the histochemical properties of SIF- and MIF-motoneurons in and around the nIII in monkey the homologous cell groups were identified in human previously (Horn et al, 2008 ; Che Ngwa et al, 2014 ; Zeeh et al, 2015 ). Thereby, an updated topographical map of the oculomotor nucleus has been created (Che Ngwa et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of Functional Cell Groups in the Abducens Nucleus of Monkey and Human by Perineuronal Nets and Choline Acetyltransferase Immunolabeling

Horn

Horng²,

Buresch

et al. 2018

Front. Neuroanat.

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The abducens nucleus (nVI) contains several functional cell groups: motoneurons of the singly-innervated twitch muscle fibers (SIF) and those of the multiply-innervated muscle fibers (MIF) of the lateral rectus muscle (LR), internuclear neurons (INTs) projecting to the contralateral oculomotor nucleus (nIII) and paramedian tract-neurons (PMT) that receive input from premotor neurons of the oculomotor system and project to the floccular region. In monkey, these cell populations can be delineated by their chemical signature. For correlative clinico-pathological studies the identification of the homologous cell groups in the human nVI are required. In this study, we plotted the distribution of these populations in monkey nVI by combined tract-tracing and immunohistochemical staining facilitating the identification of homologous cell groups in man. Paraffin sections of two Rhesus monkeys fixed with 4% paraformaldhehyde and immunostained with antibodies directed against choline acetyltransferase (ChAT) as marker enzyme for cholinergic neurons and chondroitin sulfate proteoglycan (CSPG) to detect perineuronal nets (PNs) revealed four neuron populations in nVI with different chemical signatures: ChAT-positive and CSPG-positive SIF motoneurons, ChAT-positive, but CSPG-negative MIF motoneurons, and ChAT-negative neurons with prominent PNs that were considered as INTs. This was confirmed by combined immunofluorescence labeling of cholera toxin subunit B (CTB) or wheat germ agglutinin (WGA) and ChAT or CSPG in nVI sections from cases with tracer injections into nIII. In the rostral part of nVI and at its medial border, populations of ChAT-negative groups with weak CSPG-staining, but with strong acetylcholinesterase (AChE) activity, were identified as PMT cell groups by correlating them with the location of anterograde tracer labeling from INTs in nIII. Applying ChAT- and CSPG-immunostaining as well as AChE staining to human brainstem sections four neuron groups with the same chemical signature as those in monkey could be identified in and around the nVI in human. In conclusion, the distribution of nVI neuron populations was identified in human based on findings in monkey utilizing their markers for cholinergic neurons and their different ensheathment by PNs of the extracellular matrix.

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“…In additional sections cholinergic neurons were detected by immunostaining for choline acetyltransferase (ChAT) as described previously [30]. To confirm the presence of GABAergic neurons in the Y-group, sections that had been immunostained with sheep anti-GAD [31] or mouse anti- [7]GABA [32] from previous studies were evaluated [33,34].…”

Section: Immunofluorescence Staining For Different Markersmentioning

confidence: 99%

Histochemical Characterization of the Vestibular Y-Group in Monkey

2020

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The Y-group plays an important role in the generation of upward smooth pursuit eye movements and contributes to the adaptive properties of the vertical vestibulo-ocular reflex. Malfunction of this circuitry may cause eye movement disorders, such as downbeat nystagmus. To characterize the neuron populations in the Y-group, we performed immunostainings for cellular proteins related to firing characteristics and transmitters (calretinin, GABA-related proteins and ion channels) in brainstem sections of macaque monkeys that had received tracer injections into the oculomotor nucleus. Two histochemically different populations of premotor neurons were identified: The calretinin-positive population represents the excitatory projection to contralateral upgaze motoneurons, whereas the GABAergic population represents the inhibitory projection to ipsilateral downgaze motoneurons. Both populations receive a strong supply by GABAergic nerve endings most likely originating from floccular Purkinje cells. All premotor neurons express nonphosphorylated neurofilaments and are ensheathed by strong perineuronal nets. In addition, they contain the voltage-gated potassium channels Kv1.1 and Kv3.1b which suggests biophysical similarities to high-activity premotor neurons of vestibular and oculomotor systems. The premotor neurons of Y-group form a homogenous population with histochemical characteristics compatible with fast-firing projection neurons that can also undergo plasticity and contribute to motor learning as found for the adaptation of the vestibulo-ocular reflex in response to visual-vestibular mismatch stimulation. The histochemical characterization of premotor neurons in the Y-group allows the identification of the homologue cell groups in human, including their transmitter inputs and will serve as basis for correlated anatomical-neuropathological studies of clinical cases with downbeat nystagmus.

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

Cited by 11 publications

References 107 publications

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

Identification of Functional Cell Groups in the Abducens Nucleus of Monkey and Human by Perineuronal Nets and Choline Acetyltransferase Immunolabeling

Histochemical Characterization of the Vestibular Y-Group in Monkey

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