Calretinin as a marker for premotor neurons involved in upgaze in human brainstem

Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomo...

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Main Authors: Christopher eAdamczyk, Michael eStrupp, Klaus eJahn, Anja Kerstin Ellen Horn
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-12-01
Series:Frontiers in Neuroanatomy
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00153/full
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author Christopher eAdamczyk
Michael eStrupp
Michael eStrupp
Klaus eJahn
Klaus eJahn
Anja Kerstin Ellen Horn
Anja Kerstin Ellen Horn
author_facet Christopher eAdamczyk
Michael eStrupp
Michael eStrupp
Klaus eJahn
Klaus eJahn
Anja Kerstin Ellen Horn
Anja Kerstin Ellen Horn
author_sort Christopher eAdamczyk
collection DOAJ
description Eye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of calretinin input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and calretinin may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and calretinin positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan component of perineuronal nets, parvalbumin or calretinin and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without calretinin coexpression, which were intermingled. The parvalbumin/calretinin positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking calretinin are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a subpopulation. Calretinin-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homologue premotor neurons described in monkey, projecting to superior rectus and inferior oblique motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and calretinin may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.
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spelling doaj.art-154f64fa2454419982e45e14ab6d1ac72022-12-22T00:53:47ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292015-12-01910.3389/fnana.2015.00153172216Calretinin as a marker for premotor neurons involved in upgaze in human brainstemChristopher eAdamczyk0Michael eStrupp1Michael eStrupp2Klaus eJahn3Klaus eJahn4Anja Kerstin Ellen Horn5Anja Kerstin Ellen Horn6Ludwig-Maximlians UniversityLudwig-Maximlians UniversityLudwig-Maximilians UniversitySchön KlinikLudwig-Maximilians UniversityLudwig-Maximilians UniversityLudwig-Maximilians UniversityEye movements are generated by different premotor pathways. Damage to them can cause specific deficits of eye movements, such as saccades. For correlative clinico-anatomical post-mortem studies of cases with eye movement disorders it is essential to identify the functional cell groups of the oculomotor system in the human brain by marker proteins. Based on monkey studies, the premotor neurons of the saccadic system can be identified by the histochemical markers parvalbumin and perineuronal nets in humans. These areas involve the interstitial nucleus of Cajal (INC) and the rostral interstitial nucleus of the medial longitudinal fascicle (RIMLF), which both contain premotor neurons for upgaze and downgaze. Recent monkey and human studies revealed a selective excitatory calretinin-positive input to the motoneurons mediating upgaze, but not to those for downgaze. Three premotor regions were identified as sources of calretinin input in monkey: y-group, INC and RIMLF. These findings suggest that the expression pattern of parvalbumin and calretinin may help to identify premotor neurons involved in up- or downgaze. In a post-mortem study of five human cases without neurological diseases we investigated the y-group, INC and RIMLF for the presence of parvalbumin and calretinin positive neurons including their co-expression. Adjacent thin paraffin sections were stained for the aggrecan component of perineuronal nets, parvalbumin or calretinin and glutamate decarboxylase. The comparative analysis of scanned thin sections of INC and RIMLF revealed medium-sized parvalbumin positive neurons with and without calretinin coexpression, which were intermingled. The parvalbumin/calretinin positive neurons in both nuclei are considered as excitatory premotor upgaze neurons. Accordingly, the parvalbumin-positive neurons lacking calretinin are considered as premotor downgaze neurons in RIMLF, but may in addition include inhibitory premotor upgaze neurons in the INC as indicated by co-expression of glutamate decarboxylase in a subpopulation. Calretinin-positive neurons ensheathed by perineuronal nets in the human y-group are considered as the homologue premotor neurons described in monkey, projecting to superior rectus and inferior oblique motoneurons. In conclusion, combined immunostaining for parvalbumin, perineuronal nets and calretinin may well be suited for the specific identification and subsequent analysis of premotor upgaze pathways in clinical cases of isolated up- or downgaze deficits.http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00153/fullSaccadic eye movementsoculomotor nucleusrostral interstitial nucleus of the medial longitudinal fasciculusY-groupInterstitial nucleus of Cajal
spellingShingle Christopher eAdamczyk
Michael eStrupp
Michael eStrupp
Klaus eJahn
Klaus eJahn
Anja Kerstin Ellen Horn
Anja Kerstin Ellen Horn
Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
Frontiers in Neuroanatomy
Saccadic eye movements
oculomotor nucleus
rostral interstitial nucleus of the medial longitudinal fasciculus
Y-group
Interstitial nucleus of Cajal
title Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
title_full Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
title_fullStr Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
title_full_unstemmed Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
title_short Calretinin as a marker for premotor neurons involved in upgaze in human brainstem
title_sort calretinin as a marker for premotor neurons involved in upgaze in human brainstem
topic Saccadic eye movements
oculomotor nucleus
rostral interstitial nucleus of the medial longitudinal fasciculus
Y-group
Interstitial nucleus of Cajal
url http://journal.frontiersin.org/Journal/10.3389/fnana.2015.00153/full
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