A retinal origin of congenital nystagmus
Projectomschrijving
Tijdens beweging stabiliseren wij ogenschijnlijk moeiteloos beelden op ons netvlies door samenwerking tussen netvlies, hersenstam kernen en neuronen die de oogspieren aansturen. Storing van deze regeling kan leiden tot nystagmus: onwillekeurige, repetitieve oogbewegingen, met vaak vermindering van gezichtsscherpte. De oorzaak van nystagmus is onbekend, maar wordt meestal in de hersenen gezocht. Ons onderzoek suggereert echter dat het probleem in het netvlies ligt. We vonden in 11 baby’s met nystagmus, mutaties in “netvlies” genen. In dit project willen we: 1) oorzakelijk verband aantonen tussen mutaties in deze genen, nystagmus en verminderd zicht, 2) bepalen hoe de gestoorde verwerking in het netvlies leidt tot nystagmus en verminderde gezichtsscherpte, en 3) behandelingsmogelijkheden voor nystagmus verkennen. Het project is niet alleen van groot wetenschappelijk belang, maar het heeft ook een hoge maatschappelijke impact voor nystagmus patiënten, omdat er nu geen behandeling bestaat.
Producten
Titel: Cerebellar plasticity and associative memories are controlled by perineuronal nets.
Auteur: Carulli D, Broersen R, de Winter F, Muir EM, Meškovic M, de Waal M, de Vries S, Boele HJ, Canto CB, De Zeeuw CI, Verhaagen J.
Magazine: PNAS
Auteur: Carulli D, Broersen R, de Winter F, Muir EM, Meškovic M, de Waal M, de Vries S, Boele HJ, Canto CB, De Zeeuw CI, Verhaagen J.
Magazine: PNAS
Titel: Temporal dynamics of the cerebello-cortical convergence in ventro-lateral motor thalamus
Auteur: Carmen B. Schäfer,Zhenyu Gao,Chris I. De Zeeuw,Freek E. Hoebeek
Magazine: Journal of Physiology
Auteur: Carmen B. Schäfer,Zhenyu Gao,Chris I. De Zeeuw,Freek E. Hoebeek
Magazine: Journal of Physiology
Titel: Functional Ultrasound (fUS) During Awake Brain Surgery: The Clinical Potential of Intra-Operative Functional and Vascular Brain Mapping.
Auteur: Soloukey S, Vincent AJPE, Satoer DD, Mastik F, Smits M, Dirven CMF, Strydis C, Bosch JG, van der Steen AFW, De Zeeuw CI, Koekkoek SKE, Kruizinga P.
Magazine: Frontiers in Neuroscience
Auteur: Soloukey S, Vincent AJPE, Satoer DD, Mastik F, Smits M, Dirven CMF, Strydis C, Bosch JG, van der Steen AFW, De Zeeuw CI, Koekkoek SKE, Kruizinga P.
Magazine: Frontiers in Neuroscience
Titel: Translation information processing is regulated by protein kinase C-dependent mechanism in Purkinje cells in murine posterior vermis.
Auteur: Hernández RG, De Zeeuw CI, Zhang R, Yakusheva TA, Blazquez PM.
Magazine: PNAS
Auteur: Hernández RG, De Zeeuw CI, Zhang R, Yakusheva TA, Blazquez PM.
Magazine: PNAS
Titel: Diversity and dynamism in the cerebellum.
Auteur: De Zeeuw CI, Lisberger SG, Raymond JL.
Magazine: Nature Clinical Practice Neurology
Auteur: De Zeeuw CI, Lisberger SG, Raymond JL.
Magazine: Nature Clinical Practice Neurology
Titel: Silent-substitution stimuli silence the light responses of cones but not their output.
Auteur: Kamar S, Howlett MHC, Kamermans M.
Magazine: Journal of Vision
Auteur: Kamar S, Howlett MHC, Kamermans M.
Magazine: Journal of Vision
Titel: Impaired cerebellar Purkinje cell potentiation generates unstable spatial map orientation and inaccurate navigation.
Auteur: Lefort JM, Vincent J, Tallot L, Jarlier F, De Zeeuw CI, Rondi-Reig L, Rochefort C.
Magazine: Nature Communications
Auteur: Lefort JM, Vincent J, Tallot L, Jarlier F, De Zeeuw CI, Rondi-Reig L, Rochefort C.
Magazine: Nature Communications
Titel: A cortico-cerebellar loop for motor planning.
Auteur: Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw CI, Li N.
Magazine: Nature
Auteur: Gao Z, Davis C, Thomas AM, Economo MN, Abrego AM, Svoboda K, De Zeeuw CI, Li N.
Magazine: Nature
Titel: Variability and directionality of inferior olive neuron dendrites revealed by detailed 3D characterization of an extensive morphological library
Auteur: Vrieler N, Loyola S, Yarden-Rabinowitz Y, Hoogendorp J, Medvedev N, Hoogland TM, De Zeeuw CI, De Schutter E, Yarom Y, Negrello M, Torben-Nielsen B, Uusisaari MY.
Magazine: Brain Structure and Function
Auteur: Vrieler N, Loyola S, Yarden-Rabinowitz Y, Hoogendorp J, Medvedev N, Hoogland TM, De Zeeuw CI, De Schutter E, Yarom Y, Negrello M, Torben-Nielsen B, Uusisaari MY.
Magazine: Brain Structure and Function
Titel: TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells.
Auteur: Wu B, Blot FG, Wong AB, Osório C, Adolfs Y, Pasterkamp RJ, Hartmann J, Becker EB, Boele HJ, De Zeeuw CI, Schonewille M.
Magazine: eLife
Auteur: Wu B, Blot FG, Wong AB, Osório C, Adolfs Y, Pasterkamp RJ, Hartmann J, Becker EB, Boele HJ, De Zeeuw CI, Schonewille M.
Magazine: eLife
Titel: Inactive Atm abrogates DSB repair in mouse cerebellum more than does Atm loss, without causing a neurological phenotype.
Auteur: Tal E, Alfo M, Zha S, Barzilai A, De Zeeuw CI, Ziv Y, Shiloh Y.
Magazine: DNA Repair
Auteur: Tal E, Alfo M, Zha S, Barzilai A, De Zeeuw CI, Ziv Y, Shiloh Y.
Magazine: DNA Repair
Titel: Degenerated Cones in Cultured Human Retinas Can Successfully Be Optogenetically Reactivated.
Auteur: Kamar S, Howlett MHC, Klooster J, Graaff W, Csikós T, Rabelink MJWE, Hoeben RC, Kamermans M.
Magazine: International Journal of Molecular Sciences
Auteur: Kamar S, Howlett MHC, Klooster J, Graaff W, Csikós T, Rabelink MJWE, Hoeben RC, Kamermans M.
Magazine: International Journal of Molecular Sciences
Titel: Sleep deprivation directly following eyeblink-conditioning impairs memory consolidation.
Auteur: De Zeeuw CI, Canto CB.
Magazine: Neurobiology Learning and Memory
Auteur: De Zeeuw CI, Canto CB.
Magazine: Neurobiology Learning and Memory
Titel: Pavlovian eyeblink conditioning is severely impaired in tottering mice.
Auteur: de Oude NL, Hoebeek FE, Ten Brinke MM, de Zeeuw CI, Boele HJ.
Magazine: Journal of Neurophysiology
Auteur: de Oude NL, Hoebeek FE, Ten Brinke MM, de Zeeuw CI, Boele HJ.
Magazine: Journal of Neurophysiology
Titel: Region-specific preservation of Purkinje cell morphology and motor behavior in the ATXN1[82Q] mouse model of spinocerebellar ataxia 1.
Auteur: White JJ, Bosman LWJ, Blot FGC, Osório C, Kuppens BW, Krijnen WHJJ, Andriessen C, De Zeeuw CI, Jaarsma D, Schonewille M.
Magazine: Brain Pathology
Auteur: White JJ, Bosman LWJ, Blot FGC, Osório C, Kuppens BW, Krijnen WHJJ, Andriessen C, De Zeeuw CI, Jaarsma D, Schonewille M.
Magazine: Brain Pathology
Titel: Generation of an Atxn2-CAG100 knock-in mouse reveals N-acetylaspartate production deficit due to early Nat8l dysregulation.
Auteur: Sen NE, Canet-Pons J, Halbach MV, Arsovic A, Pilatus U, Chae WH, Kaya ZE, Seidel K, Rollmann E, Mittelbronn M, Meierhofer D, De Zeeuw CI, Bosman LWJ, Gispert S, Auburger G.
Magazine: Neurobiology of Disease
Auteur: Sen NE, Canet-Pons J, Halbach MV, Arsovic A, Pilatus U, Chae WH, Kaya ZE, Seidel K, Rollmann E, Mittelbronn M, Meierhofer D, De Zeeuw CI, Bosman LWJ, Gispert S, Auburger G.
Magazine: Neurobiology of Disease
Titel: Sustained effects of prior red light on pupil diameter and vigilance during subsequent darkness.
Auteur: van der Meijden WP, Te Lindert BHW, Ramautar JR, Wei Y, Coppens JE, Kamermans M, Cajochen C, Bourgin P, Van Someren EJW.
Magazine: Proceedings of the Royal Society B (Biological Sciences)
Auteur: van der Meijden WP, Te Lindert BHW, Ramautar JR, Wei Y, Coppens JE, Kamermans M, Cajochen C, Bourgin P, Van Someren EJW.
Magazine: Proceedings of the Royal Society B (Biological Sciences)
Titel: SK2 channels in cerebellar Purkinje cells contribute to excitability modulation in motor-learning-specific memory traces.
Auteur: Grasselli G, Boele HJ, Titley HK, Bradford N, van Beers L, Jay L, Beekhof GC, Busch SE, De Zeeuw CI, Schonewille M, Hansel C.
Magazine: PLoS Biology
Auteur: Grasselli G, Boele HJ, Titley HK, Bradford N, van Beers L, Jay L, Beekhof GC, Busch SE, De Zeeuw CI, Schonewille M, Hansel C.
Magazine: PLoS Biology
Titel: Impact of parallel fiber to Purkinje cell long-term depression is unmasked in absence of inhibitory input.
Auteur: Boele HJ, Peter S, Ten Brinke MM, Verdonschot L, IJpelaar ACH, Rizopoulos D, Gao Z, Koekkoek SKE, De Zeeuw CI.
Magazine: SCIENCE ADVANCES
Auteur: Boele HJ, Peter S, Ten Brinke MM, Verdonschot L, IJpelaar ACH, Rizopoulos D, Gao Z, Koekkoek SKE, De Zeeuw CI.
Magazine: SCIENCE ADVANCES
Titel: Quasiperiodic rhythms of the inferior olive.
Auteur: Negrello M, Warnaar P, Romano V, Owens CB, Lindeman S, Iavarone E, Spanke JK, Bosman LWJ, De Zeeuw CI.
Magazine: PLoS Computational Biology
Auteur: Negrello M, Warnaar P, Romano V, Owens CB, Lindeman S, Iavarone E, Spanke JK, Bosman LWJ, De Zeeuw CI.
Magazine: PLoS Computational Biology
Titel: An Alternative Splice Variant of Zebrafish Cx52.6 is Expressed in Retinal Horizontal Cells.
Auteur: Greb H, Klaassen LJ, Schultz K, Kamermans M, Zoidl G, Weiler R, Janssen-Bienhold U.
Magazine: Neuroscience
Auteur: Greb H, Klaassen LJ, Schultz K, Kamermans M, Zoidl G, Weiler R, Janssen-Bienhold U.
Magazine: Neuroscience
Titel: Neurons of the inferior olive respond to broad classes of sensory input while subject to homeostatic control.
Auteur: Ju C, Bosman LWJ, Hoogland TM, Velauthapillai A, Murugesan P, Warnaar P, van Genderen RM, Negrello M, De Zeeuw CI.
Magazine: Journal of Physiology
Auteur: Ju C, Bosman LWJ, Hoogland TM, Velauthapillai A, Murugesan P, Warnaar P, van Genderen RM, Negrello M, De Zeeuw CI.
Magazine: Journal of Physiology
Titel: How the COVID-19 pandemic highlights the necessity of animal research.
Auteur: Genzel L, Adan R, Berns A, van den Beucken JJJP, Blokland A, Boddeke EHWGM, Bogers WM, Bontrop R, Bulthuis R, Bousema T, Clevers H, Coenen TCJJ, van Dam AM, Deen PMT, van Dijk KW, Eggen BJL, Elgersma Y, Erdogan I, Englitz B, Fentener van Vlissingen JM, la Fleur S, Fouchier R, Fitzsimons CP, Frieling W, Haagmans B, Heesters BA, Henckens MJAG, Herfst S, Hol E, van den Hove D, de Jonge MI, Jonkers J, Joosten LAB, Kalsbeek A, Kamermans M, Kampinga HH, Kas MJ, Keijer J, Kersten S, Kiliaan AJ, Kooij T
Magazine: Current Biology
Auteur: Genzel L, Adan R, Berns A, van den Beucken JJJP, Blokland A, Boddeke EHWGM, Bogers WM, Bontrop R, Bulthuis R, Bousema T, Clevers H, Coenen TCJJ, van Dam AM, Deen PMT, van Dijk KW, Eggen BJL, Elgersma Y, Erdogan I, Englitz B, Fentener van Vlissingen JM, la Fleur S, Fouchier R, Fitzsimons CP, Frieling W, Haagmans B, Heesters BA, Henckens MJAG, Herfst S, Hol E, van den Hove D, de Jonge MI, Jonkers J, Joosten LAB, Kalsbeek A, Kamermans M, Kampinga HH, Kas MJ, Keijer J, Kersten S, Kiliaan AJ, Kooij T
Magazine: Current Biology
Titel: Differential Coding Strategies in Glutamatergic and GABAergic Neurons in the Medial Cerebellar Nucleus.
Auteur: Özcan OO, Wang X, Binda F, Dorgans K, De Zeeuw CI, Gao Z, Aertsen A, Kumar A, Isope P.
Magazine: The Journal of Neuroscience
Auteur: Özcan OO, Wang X, Binda F, Dorgans K, De Zeeuw CI, Gao Z, Aertsen A, Kumar A, Isope P.
Magazine: The Journal of Neuroscience
Titel: Usherin defects lead to early-onset retinal dysfunction in zebrafish.
Auteur: Dona M, Slijkerman R, Lerner K, Broekman S, Wegner J, Howat T, Peters T, Hetterschijt L, Boon N, de Vrieze E, Sorusch N, Wolfrum U, Kremer H, Neuhauss S, Zang J, Kamermans M, Westerfield M, Phillips J, van Wijk E.
Magazine: Experimental Eye Research
Auteur: Dona M, Slijkerman R, Lerner K, Broekman S, Wegner J, Howat T, Peters T, Hetterschijt L, Boon N, de Vrieze E, Sorusch N, Wolfrum U, Kremer H, Neuhauss S, Zang J, Kamermans M, Westerfield M, Phillips J, van Wijk E.
Magazine: Experimental Eye Research
Titel: WhiskEras: A New Algorithm for Accurate Whisker Tracking.
Auteur: Betting JLF, Romano V, Al-Ars Z, Bosman LWJ, Strydis C, De Zeeuw CI.
Magazine: Frontiers in Cellular Neuroscience
Auteur: Betting JLF, Romano V, Al-Ars Z, Bosman LWJ, Strydis C, De Zeeuw CI.
Magazine: Frontiers in Cellular Neuroscience
Titel: Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity.
Auteur: Romano V, De Propris L, Bosman LW, Warnaar P, Ten Brinke MM, Lindeman S, Ju C, Velauthapillai A, Spanke JK, Middendorp Guerra E, Hoogland TM, Negrello M, D'Angelo E, De Zeeuw CI.
Magazine: eLife
Auteur: Romano V, De Propris L, Bosman LW, Warnaar P, Ten Brinke MM, Lindeman S, Ju C, Velauthapillai A, Spanke JK, Middendorp Guerra E, Hoogland TM, Negrello M, D'Angelo E, De Zeeuw CI.
Magazine: eLife
Titel: AMPAR Auxiliary Protein SHISA6 Facilitates Purkinje Cell Synaptic Excitability and Procedural Memory Formation.
Auteur: Peter S, Urbanus BHA, Klaassen RV, Wu B, Boele HJ, Azizi S, Slotman JA, Houtsmuller AB, Schonewille M, Hoebeek FE, Spijker S, Smit AB, De Zeeuw CI.
Magazine: Cell Reports
Auteur: Peter S, Urbanus BHA, Klaassen RV, Wu B, Boele HJ, Azizi S, Slotman JA, Houtsmuller AB, Schonewille M, Hoebeek FE, Spijker S, Smit AB, De Zeeuw CI.
Magazine: Cell Reports
Titel: Action perception recruits the cerebellum and is impaired in patients with spinocerebellar ataxia.
Auteur: Abdelgabar AR, Suttrup J, Broersen R, Bhandari R, Picard S, Keysers C, De Zeeuw CI, Gazzola V.
Magazine: Brain Communications
Auteur: Abdelgabar AR, Suttrup J, Broersen R, Bhandari R, Picard S, Keysers C, De Zeeuw CI, Gazzola V.
Magazine: Brain Communications
Titel: Nystagmus in patients with congenital stationary night blindness (CSNB) originates from synchronously firing retinal ganglion cells.
Auteur: Winkelman BHJ, Howlett MHC, Hölzel MB, Joling C, Fransen KH, Pangeni G, Kamermans S, Sakuta H, Noda M, Simonsz HJ, McCall MA, De Zeeuw CI, Kamermans M.
Magazine: PLoS Biology
Auteur: Winkelman BHJ, Howlett MHC, Hölzel MB, Joling C, Fransen KH, Pangeni G, Kamermans S, Sakuta H, Noda M, Simonsz HJ, McCall MA, De Zeeuw CI, Kamermans M.
Magazine: PLoS Biology
Titel: Cerebellar Purkinje cells can differentially modulate coherence between sensory and motor cortex depending on region and behavior
Auteur: Lindeman S, Hong S, Kros L, Mejias JF, Romano V, Oostenveld R, Negrello M, Bosman LWJ, De Zeeuw CI.
Magazine: PNAS
Auteur: Lindeman S, Hong S, Kros L, Mejias JF, Romano V, Oostenveld R, Negrello M, Bosman LWJ, De Zeeuw CI.
Magazine: PNAS
Titel: NINscope, a versatile miniscope for multi-region circuit investigations.
Auteur: de Groot A, van den Boom BJ, van Genderen RM, Coppens J, van Veldhuijzen J, Bos J, Hoedemaker H, Negrello M, Willuhn I, De Zeeuw CI, Hoogland TM.
Magazine: eLife
Auteur: de Groot A, van den Boom BJ, van Genderen RM, Coppens J, van Veldhuijzen J, Bos J, Hoedemaker H, Negrello M, Willuhn I, De Zeeuw CI, Hoogland TM.
Magazine: eLife
Titel: A FN-MdV pathway and its role in cerebellar multimodular control of sensorimotor behavior.
Auteur: Wang X, Yu SY, Ren Z, De Zeeuw CI, Gao Z.
Magazine: Nature Communications
Auteur: Wang X, Yu SY, Ren Z, De Zeeuw CI, Gao Z.
Magazine: Nature Communications
Titel: Functional Convergence of Autonomic and Sensorimotor Processing in the Lateral Cerebellum.
Auteur: Romano V, Reddington AL, Cazzanelli S, Mazza R, Ma Y, Strydis C, Negrello M, Bosman LWJ, De Zeeuw CI.
Magazine: Cell Reports
Auteur: Romano V, Reddington AL, Cazzanelli S, Mazza R, Ma Y, Strydis C, Negrello M, Bosman LWJ, De Zeeuw CI.
Magazine: Cell Reports
Titel: Glissades Are Altered by Lesions to the Oculomotor Vermis but Not by Saccadic Adaptation.
Auteur: Flierman NA, Ignashchenkova A, Negrello M, Thier P, De Zeeuw CI, Badura A.
Magazine: Frontiers in Behavioral Neuroscience
Auteur: Flierman NA, Ignashchenkova A, Negrello M, Thier P, De Zeeuw CI, Badura A.
Magazine: Frontiers in Behavioral Neuroscience
Titel: Bidirectional learning in upbound and downbound microzones of the cerebellum
Auteur: De Zeeuw CI.
Magazine: Nature Reviews Neuroscience
Auteur: De Zeeuw CI.
Magazine: Nature Reviews Neuroscience
Titel: High Contrast Allows the Retina to Compute More Than Just Contrast.
Auteur: Yedutenko M, Howlett MHC, Kamermans M.
Magazine: Frontiers Cell Neuroscience
Auteur: Yedutenko M, Howlett MHC, Kamermans M.
Magazine: Frontiers Cell Neuroscience
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Samenvatting van de aanvraag
One of the amazing abilities of our brain is to stabilize our sensory input in order to facilitate perception. For example, we can stabilize images on the retina when moving around in our environment. This is accomplished by close interactions between the sensory input from the retina, the accessory optic system (AOS), the vestibulo-cerebellar system and the oculomotor neurons that drive the eye muscles. Various feedback loops and adaptive mechanisms ensure that retinal slip, i.e. retinal image motion, is minimized. Malfunction of this control system can lead to nystagmus (i.e. involuntary repetitive uncontrolled eye-movements), which often severely affects visual acuity (http://www.nystagmusnet.org/cms/index.php/nystagmus).
There are many forms of nystagmus (prevalence approx., 0.2%) with many different causes. Nystagmus can be infantile or develop later in life by, for instance, neurological disorders. Nystagmus is often accompanied by a reduced visual acuity. The relation between these two symptoms is an issue of debate. Understanding the pathophysiological mechanism of nystagmus and the related reduced visual acuity is therefore crucial for developing therapeutical strategies for nystagmus patients.
The exact causes of congenital nystagmus are largely unknown, but it is generally assumed that congenital nystagmus originates from problems in the AOS, vestibulo-cerebellar and/or oculomotor system. However, our recent research indicates that, at least, some types of congenital nystagmus have a retinal origin. We recently examined 11 infant boys of 2-3 months who presented with a tonic downgaze of both eyes, a chin-up head posture and a rapid horizontal congenital nystagmus. These infants also developed a gaze-evoked upbeat nystagmus and reduced visual acuity. Because all patients had congenital stationary night blindness (CSNB), a hereditary retinal disorder, we called this syndrome Nightblindness-Associated Transient Tonic Downgaze (NATTD). We determined the genetic background of NATTD and found mutations in NYX, CACNA1F or GPR179. This combination of genes is highly specific for the photoreceptor to ON-bipolar cell synapse (ON-BCs). NYX and GPR179 are located post-synaptically at the ON-BC synapse, whereas CACNA1F is expressed pre-synaptically at this synapse. Mutations in any of these genes abolish ON-BC activity.
Thus, our preliminary work indicates that malfunctioning of retinal ON-BCs can lead to specific types of congenital nystagmus, but the precise pathophysiological mechanism remains to be elucidated. In particular, it remains to be resolved to what extent the motor (nystagmus) and sensory (vision) deficits are directly causally related or whether they reflect defects in different processes triggered by a common cause.
To understand the pathogenesis and pave the way for future therapeutic approaches, we aim to: 1) to establish a relation between the mutations affecting retinal ON-BC function and congenital nystagmus (NATTD) and reduced visual acuity; 2) to elucidate the consequences of disturbed retinal signalling for eye-movements, visual acuity and information processing by the AOS and the vestibulo-cerebellum; and 3) to translate the results obtained in the animal studies to the human condition by exploring possible genetic, pharmacological, optogenetic and/or optical therapeutical interventions. Achieving these key objectives will provide insight into the mechanisms underlying this type of congenital nystagmus and concomitant reduced visual acuity. This may offer possibilities to treat the perceptual burden of nystagmus for which no treatment is presently available.