Skip to main content
Top
Published in: The Cerebellum 5/2021

Open Access 01-10-2021 | ORIGINAL PAPER

Histochemical Characterization of the Vestibular Y-Group in Monkey

Authors: Christina Zeeh, Ümit S. Mayadali, Anja K.E. Horn

Published in: The Cerebellum | Issue 5/2021

Login to get access

Abstract

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.
Literature
1.
go back to reference Chubb MC, Fuchs AF. Contribution of y group of vestibular nuclei and dentate nucleus of cerebellum to generation of vertical smooth eye movements. J Neurophysiol. 1982;48:75–99.PubMed Chubb MC, Fuchs AF. Contribution of y group of vestibular nuclei and dentate nucleus of cerebellum to generation of vertical smooth eye movements. J Neurophysiol. 1982;48:75–99.PubMed
2.
3.
go back to reference Leigh RJ, Zee DS. The neurology of eye movements. Oxford. Oxford University Press; 2015. Leigh RJ, Zee DS. The neurology of eye movements. Oxford. Oxford University Press; 2015.
4.
go back to reference Partsalis AM, Zhang Y, Highstein SM. Dorsal Y group in the squirrel monkey. I. Neuronal responses during rapid and long-term modifications of the vertical VOR. J Neurophysiol. 1995;73:615–31.PubMed Partsalis AM, Zhang Y, Highstein SM. Dorsal Y group in the squirrel monkey. I. Neuronal responses during rapid and long-term modifications of the vertical VOR. J Neurophysiol. 1995;73:615–31.PubMed
5.
go back to reference Marti S, Straumann D, Büttner U. Glasauer S. A model-based theory on the origin of downbeat nystagmus. Exp Brain Res. 2008; 188:613–31. Marti S, Straumann D, Büttner U. Glasauer S. A model-based theory on the origin of downbeat nystagmus. Exp Brain Res. 2008; 188:613–31.
6.
go back to reference Goldberg JM, Wilson VJ, Cullen KE, Angelaki DE, Broussard DM, Büttner-Ennever JA, et al. The vestibular system. A sixth sense. Oxford: Oxford University Press; 2012. Goldberg JM, Wilson VJ, Cullen KE, Angelaki DE, Broussard DM, Büttner-Ennever JA, et al. The vestibular system. A sixth sense. Oxford: Oxford University Press; 2012.
7.
go back to reference Gacek RR. Location of brain stem neurons projecting to the oculomotor nucleus in the cat. Exp Neurol. 1977;57:725–49.PubMed Gacek RR. Location of brain stem neurons projecting to the oculomotor nucleus in the cat. Exp Neurol. 1977;57:725–49.PubMed
8.
go back to reference Highstein SM, Holstein GR. The anatomy of the vestibular nuclei. Prog Brain Res. 2006;151:157–203.PubMed Highstein SM, Holstein GR. The anatomy of the vestibular nuclei. Prog Brain Res. 2006;151:157–203.PubMed
9.
go back to reference Büttner-Ennever JA, Horn AKE. Olszewski and Baxter’s cytoarchitecture of the human brainstem. Basel, Freiburg: Karger; 2014. Büttner-Ennever JA, Horn AKE. Olszewski and Baxter’s cytoarchitecture of the human brainstem. Basel, Freiburg: Karger; 2014.
10.
go back to reference Gacek RR. The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol. 1969;254:1–66. Gacek RR. The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol. 1969;254:1–66.
11.
go back to reference Kevetter GA, Perachio AA. Distribution of vestibular afferents that innervate the sacculus and posterior canal in gerbil. J Comp Neurol. 1986;254:410–24.PubMed Kevetter GA, Perachio AA. Distribution of vestibular afferents that innervate the sacculus and posterior canal in gerbil. J Comp Neurol. 1986;254:410–24.PubMed
12.
go back to reference Carleton SC, Carpenter MB. Distribution of primary vesibular fibers in the brainstem and cerebellum of the monkey. Brain Res. 1984;294:281–98.PubMed Carleton SC, Carpenter MB. Distribution of primary vesibular fibers in the brainstem and cerebellum of the monkey. Brain Res. 1984;294:281–98.PubMed
13.
go back to reference Gacek RR. Location of commissural neurons in the vestibular nuclei of the cat. Exp Neurol. 1978;59:479–91.PubMed Gacek RR. Location of commissural neurons in the vestibular nuclei of the cat. Exp Neurol. 1978;59:479–91.PubMed
14.
go back to reference Carpenter MB, Cowie RJ. Connections and oculomotor projections of the superior vestibular nucleus and cell group 'y'. Brain Res. 1985;336:265–87.PubMed Carpenter MB, Cowie RJ. Connections and oculomotor projections of the superior vestibular nucleus and cell group 'y'. Brain Res. 1985;336:265–87.PubMed
15.
go back to reference Pompeiano O, Mergner T, Corvaja N. Commissural, perihypoglossal and reticular afferent projections to the vestibular nuclei in the cat: an experimental anatomical study with horseradish peroxidase. Arch Ital Biol. 1978;116:130–72.PubMed Pompeiano O, Mergner T, Corvaja N. Commissural, perihypoglossal and reticular afferent projections to the vestibular nuclei in the cat: an experimental anatomical study with horseradish peroxidase. Arch Ital Biol. 1978;116:130–72.PubMed
17.
go back to reference Nagao S, Kitamura T, Nakamura N, Hiramatsu T, Yamada J. Differences of the primate flocculus and ventral paraflocculus in the mossy and climbing fiber input organization. J Comp Neurol. 1997;382:480–98.PubMed Nagao S, Kitamura T, Nakamura N, Hiramatsu T, Yamada J. Differences of the primate flocculus and ventral paraflocculus in the mossy and climbing fiber input organization. J Comp Neurol. 1997;382:480–98.PubMed
18.
go back to reference Langer TP, Fuchs AF, Scudder CA, Chubb MC. Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase. J Comp Neurol. 1985;235:1–25.PubMed Langer TP, Fuchs AF, Scudder CA, Chubb MC. Afferents to the flocculus of the cerebellum in the rhesus macaque as revealed by retrograde transport of horseradish peroxidase. J Comp Neurol. 1985;235:1–25.PubMed
19.
go back to reference Blazquez P, Partsalis A, Gerrits NM, Highstein SM. Input of anterior and posterior semicircular canal interneurons encoding head-velocity to the dorsal Y group of the vestibular nuclei. J Neurophysiol. 2000;83:2891–904.PubMed Blazquez P, Partsalis A, Gerrits NM, Highstein SM. Input of anterior and posterior semicircular canal interneurons encoding head-velocity to the dorsal Y group of the vestibular nuclei. J Neurophysiol. 2000;83:2891–904.PubMed
20.
go back to reference Blanks RHI, Precht W, Torigoe Y. Afferent projections to the cerebellar flocculus in the pigmented rat demonstrated by retrograde transport of horseradish peroxidase. Exp Brain Res. 1983;52:293–306.PubMed Blanks RHI, Precht W, Torigoe Y. Afferent projections to the cerebellar flocculus in the pigmented rat demonstrated by retrograde transport of horseradish peroxidase. Exp Brain Res. 1983;52:293–306.PubMed
21.
go back to reference Partsalis AM, Zhang Y, Highstein SM. Dorsal Y group in the squirrel monkey. II. Contribution of the cerebellar flocculus to neuronal responses in normal and adapted animals. J Neurophysiol. 1995;73:632–50.PubMed Partsalis AM, Zhang Y, Highstein SM. Dorsal Y group in the squirrel monkey. II. Contribution of the cerebellar flocculus to neuronal responses in normal and adapted animals. J Neurophysiol. 1995;73:632–50.PubMed
22.
go back to reference Langer TP, Fuchs AF, Chubb MC, Scudder CA, Lisberger SG. Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase. J Comp Neurol. 1985;235:26–37.PubMed Langer TP, Fuchs AF, Chubb MC, Scudder CA, Lisberger SG. Floccular efferents in the rhesus macaque as revealed by autoradiography and horseradish peroxidase. J Comp Neurol. 1985;235:26–37.PubMed
23.
go back to reference Graybiel AM, Hartwieg EA. Some afferent connections of the oculomotor complex in the cat: an experimental study with tracer techniques. Brain Res. 1974;81:543–51.PubMed Graybiel AM, Hartwieg EA. Some afferent connections of the oculomotor complex in the cat: an experimental study with tracer techniques. Brain Res. 1974;81:543–51.PubMed
24.
go back to reference Steiger HJ, Büttner-Ennever JA. Oculomotor nucleus afferents in the monkey demonstrated with horseradish peroxidase. Brain Res. 1979;160:1–15. Steiger HJ, Büttner-Ennever JA. Oculomotor nucleus afferents in the monkey demonstrated with horseradish peroxidase. Brain Res. 1979;160:1–15.
25.
go back to reference Sato Y, Kawasaki T. Organization of maculo-ocular pathways via y-group nucleus and its relevance to cerebellar flocculus in cats. Physiologist. 1987;30:S77–80.PubMed Sato Y, Kawasaki T. Organization of maculo-ocular pathways via y-group nucleus and its relevance to cerebellar flocculus in cats. Physiologist. 1987;30:S77–80.PubMed
26.
go back to reference Zeeh C, Hess BJ, Horn AKE. Calretinin inputs are confined to motoneurons for upward eye movements in monkey. J Comp Neurol. 2013;521:3154–66. Zeeh C, Hess BJ, Horn AKE. Calretinin inputs are confined to motoneurons for upward eye movements in monkey. J Comp Neurol. 2013;521:3154–66.
27.
go back to reference Ahlfeld J, Mustari M, Horn AKE. Sources of calretinin inputs to motoneurons of extraocular muscles involved in upgaze. Ann N Y Acad Sci. 2011;1233:91–9.PubMedPubMedCentral Ahlfeld J, Mustari M, Horn AKE. Sources of calretinin inputs to motoneurons of extraocular muscles involved in upgaze. Ann N Y Acad Sci. 2011;1233:91–9.PubMedPubMedCentral
28.
go back to reference Lienbacher K, Mustari M, Ying HS, Büttner-Ennever JA, Horn AKE. Do palisade endings in extraocular muscles arise from neurons in the motor nuclei? Invest Ophthalmol Vis Sci. 2011;52:2510–19. Lienbacher K, Mustari M, Ying HS, Büttner-Ennever JA, Horn AKE. Do palisade endings in extraocular muscles arise from neurons in the motor nuclei? Invest Ophthalmol Vis Sci. 2011;52:2510–19.
32.
go back to reference Holstein GR, Martinelli GP, Degen JW, Cohen B. GABAergic neurons in the primate vestibular nuclei. Ann N Y Acad Sci. 1996;781:443–57.PubMed Holstein GR, Martinelli GP, Degen JW, Cohen B. GABAergic neurons in the primate vestibular nuclei. Ann N Y Acad Sci. 1996;781:443–57.PubMed
33.
go back to reference Horn AKE, Helmchen C, Wahle P. GABAergic neurons in the rostral mesencephalon of the macaque monkey that control vertical eye movements. Ann N Y Acad Sci. 2003;1004:19–28.PubMed Horn AKE, Helmchen C, Wahle P. GABAergic neurons in the rostral mesencephalon of the macaque monkey that control vertical eye movements. Ann N Y Acad Sci. 2003;1004:19–28.PubMed
35.
go back to reference Holstein GR. The vestibular system. In: Mai JK, Paxinos G, editors. The human nervous system. Amsterdam: Elsevier; 2012. p. 1239–69. Holstein GR. The vestibular system. In: Mai JK, Paxinos G, editors. The human nervous system. Amsterdam: Elsevier; 2012. p. 1239–69.
36.
go back to reference Langer TP. Basal interstitial nucleus of the cerebellum: cerebellar nucleus related to the flocculus. J Comp Neurol. 1985;235:38–47.PubMed Langer TP. Basal interstitial nucleus of the cerebellum: cerebellar nucleus related to the flocculus. J Comp Neurol. 1985;235:38–47.PubMed
37.
go back to reference Büttner-Ennever JA, Grob P, Akert K, Bizzini B. Transsynaptic retrograde labeling in the oculomotor system of the monkey with [125I] tetanus toxin BIIb fragment. Neurosci Lett. 1981;26:233–8.PubMed Büttner-Ennever JA, Grob P, Akert K, Bizzini B. Transsynaptic retrograde labeling in the oculomotor system of the monkey with [125I] tetanus toxin BIIb fragment. Neurosci Lett. 1981;26:233–8.PubMed
38.
go back to reference Mayadali ÜS, Lienbacher K, Mustari M, Strupp M, Horn A. Potassium channels in omnipause neurons. Prog Brain Res. 2019;249:117–23.PubMed Mayadali ÜS, Lienbacher K, Mustari M, Strupp M, Horn A. Potassium channels in omnipause neurons. Prog Brain Res. 2019;249:117–23.PubMed
41.
go back to reference Stanton GB. Afferents to oculomotor nuclei from area "Y" in Macaca mulatta: an anterograde degeneration study. J Comp Neurol. 1980;192:377–85.PubMed Stanton GB. Afferents to oculomotor nuclei from area "Y" in Macaca mulatta: an anterograde degeneration study. J Comp Neurol. 1980;192:377–85.PubMed
42.
go back to reference Wasicky R, Horn AKE, Büttner-Ennever JA. Twitch and non-twitch motoneuron subgroups of the medial rectus muscle in the oculomotor nucleus of monkeys receive different afferent projections. J Comp Neurol. 2004;479:117–29.PubMed Wasicky R, Horn AKE, Büttner-Ennever JA. Twitch and non-twitch motoneuron subgroups of the medial rectus muscle in the oculomotor nucleus of monkeys receive different afferent projections. J Comp Neurol. 2004;479:117–29.PubMed
43.
go back to reference Highstein SM. Organization of the inhibitory and excitatory vestibulo-ocular reflex pathways to the third and fourth nuclei in rabbit. Brain Res. 1971;32:218–24.PubMed Highstein SM. Organization of the inhibitory and excitatory vestibulo-ocular reflex pathways to the third and fourth nuclei in rabbit. Brain Res. 1971;32:218–24.PubMed
44.
go back to reference Mugnani E, Oertel WH. An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunocytochemistry. In: Handbook of Chemical Neuroanatomy, vol. 4; 1985. p. 436–608. Mugnani E, Oertel WH. An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunocytochemistry. In: Handbook of Chemical Neuroanatomy, vol. 4; 1985. p. 436–608.
45.
go back to reference Carpenter MB, Huang Y, Pereia AB, Hersh LB. Immunocytochemical features of the vestibular nuclei in the monkey and the cat. J Hirnforsch. 1990;31:585–99.PubMed Carpenter MB, Huang Y, Pereia AB, Hersh LB. Immunocytochemical features of the vestibular nuclei in the monkey and the cat. J Hirnforsch. 1990;31:585–99.PubMed
46.
go back to reference De Zeeuw CI, Gerrits NM, Voogd J, Leonard CS, Simpson JI. The rostral dorsal cap and ventrolateral outgrowth of the rabbit inferior olive receive a GABAergic input from dorsal group Y and the ventral dentate nucleus. J Comp Neurol. 1994;341:420–32.PubMed De Zeeuw CI, Gerrits NM, Voogd J, Leonard CS, Simpson JI. The rostral dorsal cap and ventrolateral outgrowth of the rabbit inferior olive receive a GABAergic input from dorsal group Y and the ventral dentate nucleus. J Comp Neurol. 1994;341:420–32.PubMed
47.
go back to reference Wentzel PR, Wylie DRW, Ruigrok TJH, de Zeeuw CI. Olivary projecting neurons in the nucleus prepositus hypoglossi, group y and ventral dentate nucleus do not project to the oculomotor complex in the rabbit and the rat. Neurosci Lett. 1995;190:45–8.PubMed Wentzel PR, Wylie DRW, Ruigrok TJH, de Zeeuw CI. Olivary projecting neurons in the nucleus prepositus hypoglossi, group y and ventral dentate nucleus do not project to the oculomotor complex in the rabbit and the rat. Neurosci Lett. 1995;190:45–8.PubMed
49.
go back to reference Sato Y, Kawasaki T. Target neurons of floccular caudal zone inhibition in Y-group nucleus of vestibular nuclear complex. J Neurophysiol. 1987;57:460–80.PubMed Sato Y, Kawasaki T. Target neurons of floccular caudal zone inhibition in Y-group nucleus of vestibular nuclear complex. J Neurophysiol. 1987;57:460–80.PubMed
50.
go back to reference Fortin M, Marchand R, Parent A. Calcium-binding proteins in primate cerebellum. Neurosci Res. 1998;30:155–68.PubMed Fortin M, Marchand R, Parent A. Calcium-binding proteins in primate cerebellum. Neurosci Res. 1998;30:155–68.PubMed
51.
go back to reference Sternberger LA, Sternberger NH. Monoclonal antibodies distinguish phorphorylated and non-phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci. 1983;80:6126–30.PubMedPubMedCentral Sternberger LA, Sternberger NH. Monoclonal antibodies distinguish phorphorylated and non-phosphorylated forms of neurofilaments in situ. Proc Natl Acad Sci. 1983;80:6126–30.PubMedPubMedCentral
52.
go back to reference Horn AKE, Adamcyzk C. Reticular formation - eye movements. Gaze and blinks. In: Mai JK, Paxinos G, editors. The human nervous system. Amsterdam: Elsevier; 2011. Horn AKE, Adamcyzk C. Reticular formation - eye movements. Gaze and blinks. In: Mai JK, Paxinos G, editors. The human nervous system. Amsterdam: Elsevier; 2011.
55.
go back to reference Horn AKE, Brückner G, Härtig W, Messoudi A. Saccadic omnipause and burst neurons in monkey and human are ensheathed by perineuronal nets but differ in their expression of calcium-binding proteins. J Comp Neurol. 2003;455:341–52.PubMed Horn AKE, Brückner G, Härtig W, Messoudi A. Saccadic omnipause and burst neurons in monkey and human are ensheathed by perineuronal nets but differ in their expression of calcium-binding proteins. J Comp Neurol. 2003;455:341–52.PubMed
57.
go back to reference Celio MR, Blümcke I. Perineuronal nets - a specialized form of extracellular matrix in the adult nervous system. Brain Res Rev. 1994;19:1128–45. Celio MR, Blümcke I. Perineuronal nets - a specialized form of extracellular matrix in the adult nervous system. Brain Res Rev. 1994;19:1128–45.
58.
go back to reference Härtig W, Derouiche A, Welt K, Brauer K, Grosche J, Mäder M, et al. Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations. Brain Res. 1999;842:15–29.PubMed Härtig W, Derouiche A, Welt K, Brauer K, Grosche J, Mäder M, et al. Cortical neurons immunoreactive for the potassium channel Kv3.1b subunit are predominantly surrounded by perineuronal nets presumed as a buffering system for cations. Brain Res. 1999;842:15–29.PubMed
60.
go back to reference Dulac S, Raymond JL, Sejnowski TJ, Lisberger SG. Learning and memory in the vestibulo-ocular reflex. Annu Rev Neurosci. 1995;441:18409–41. Dulac S, Raymond JL, Sejnowski TJ, Lisberger SG. Learning and memory in the vestibulo-ocular reflex. Annu Rev Neurosci. 1995;441:18409–41.
69.
go back to reference Johnston J, Forsythe ID. Kopp-Scheinpflug C. Going native: voltage-gated potassium channels controlling neuronal excitability. J Physiol. 2010;588:3187–200. Johnston J, Forsythe ID. Kopp-Scheinpflug C. Going native: voltage-gated potassium channels controlling neuronal excitability. J Physiol. 2010;588:3187–200.
71.
go back to reference Blázquez PM, Pastor AM. Cerebellar control of eye movements. In: Manto M, Schmahmann JD, Rossi F, Gruol DL, Koibuchi N, editors. Handbook of the cerebellum and cerebellar disorders. Dordrecht: Springer Netherlands; 2013. p. 1155–73. Blázquez PM, Pastor AM. Cerebellar control of eye movements. In: Manto M, Schmahmann JD, Rossi F, Gruol DL, Koibuchi N, editors. Handbook of the cerebellum and cerebellar disorders. Dordrecht: Springer Netherlands; 2013. p. 1155–73.
73.
go back to reference Bronstein AM, Miller DH, Rudge P, Kendall BE. Down beating nystagmus: magnetic resonance imaging and neuro-otological findings. J Neurol Sci. 1987;81:173–84.PubMed Bronstein AM, Miller DH, Rudge P, Kendall BE. Down beating nystagmus: magnetic resonance imaging and neuro-otological findings. J Neurol Sci. 1987;81:173–84.PubMed
Metadata
Title
Histochemical Characterization of the Vestibular Y-Group in Monkey
Authors
Christina Zeeh
Ümit S. Mayadali
Anja K.E. Horn
Publication date
01-10-2021
Publisher
Springer US
Published in
The Cerebellum / Issue 5/2021
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-020-01200-z

Other articles of this Issue 5/2021

The Cerebellum 5/2021 Go to the issue