Cerebellar extinction lesions can manifest themselves with cerebellar motor and cerebellar cognitive affective syndromes. For investigation of the functions of the cerebellum and the pathogenesis of cerebellar diseases, particularly hereditary neurodegenerative cerebellar ataxias, various cerebellar mutant mice are used. The Lurcher mouse is a model of selective olivocerebellar degeneration with early onset and rapid progress. These mice show both motor deficits as well as cognitive and behavioral changes i.e., pathological phenotype in the functional domains affected in cerebellar patients. Therefore, Lurcher mice might be considered as a tool to investigate the mechanisms of functional impairments caused by cerebellar degenerative diseases. There are, however, limitations due to the particular features of the neurodegenerative process and a lack of possibilities to examine some processes in mice. The main advantage of Lurcher mice would be the expected absence of significant neuropathologies outside the olivocerebellar system that modify the complex behavioral phenotype in less selective models. However, detailed examinations and further thorough validation of the model are needed to verify this assumption.

Department of Pathological Physiology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pathophysiology Faculty of Medicine in Pilsen Charles University alej Svobody 76 Plzen 323 00 Czech Republic

Institute of Research and Innovation in Biomedicine Rouen 76000 France

Laboratory of Neurodegenerative Disorders Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Univ Rouen Normandie Inserm Normandie Univ CBG UMR 1245 NeuroGlio Team Rouen France

Zobrazit více v PubMed

Fuentes CT, Bastian AJ. Motor cognition’ - what is it and is the cerebellum involved? Cerebellum. 2007;6:232–6. 10.1080/14734220701329268. PubMed PMC

Roostaei T, Nazeri A, Sahraian MA, Minagar A. The human cerebellum: a review of physiologic neuroanatomy. Neurol Clin. 2014;32:859–69. 10.1016/j.ncl.2014.07.013. PubMed

Rudolph S, Badura A, Lutzu S, Pathak SS, Thieme A, Verpeut JL, et al. Cognitive-Affective functions of the cerebellum. J Neurosci. 2023;43:7554–64. 10.1523/JNEUROSCI.1451-23.2023. PubMed PMC

Holmes G. The symptoms of acute cerebellar injuries due to gunshot injuries. Brain. 1917;40:461–535. 10.1093/brain/40.4.461.

Schmahmann JD, Sherman JC. Cerebellar cognitive affective syndrome. Int Rev Neurobiol. 1997;41:433–40. PubMed

Schmahmann JD, Sherman JC. The cerebellar cognitive affective syndrome. Brain. 1998;121(Pt 4):561–79. PubMed

Leisman G, Moustafa AA, Shafir T, Thinking. Walking, talking: integratory motor and cognitive brain function. Front Public Health. 2016;4:94. 10.3389/fpubh.2016.00094. PubMed PMC

Welniarz Q, Worbe Y, Gallea C. The forward model: A unifying theory for the role of the cerebellum in motor control and sense of agency. Front Syst Neurosci. 2021;15:644059. 10.3389/fnsys.2021.644059. PubMed PMC

Hoche F, Guell X, Vangel MG, Sherman JC, Schmahmann JD. The cerebellar cognitive affective/schmahmann syndrome scale. Brain. 2018;141:248–70. 10.1093/brain/awx317. PubMed PMC

Levisohn L, Cronin-Golomb A, Schmahmann JD. Neuropsychological consequences of cerebellar tumour resection in children: cerebellar cognitive affective syndrome in a paediatric population. Brain. 2000;123(Pt 5):1041–50. 10.1093/brain/123.5.1041. PubMed

Manto M, Marien P. Schmahmann’s syndrome - identification of the third cornerstone of clinical ataxiology. Cerebellum Ataxias. 2015;2:2. 10.1186/s40673-015-0023-1. PubMed PMC

Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum. 2007;6:254–67. 10.1080/14734220701490995. PubMed

Koeppen AH. The neuropathology of the adult cerebellum. Handb Clin Neurol. 2018;154:129–49. doi 10.1016/B978-0-444-63956-1.00008– 4. PubMed PMC

Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42:174–83. 10.1159/000358801. PubMed

Phillips RJS. Lurcher’, a new gene in linkage group XI of the house mouse. J Genet. 1960;57:35–42. 10.1007/BF02985337.

Hashimoto K, Ichikawa R, Takechi H, Inoue Y, Aiba A, Sakimura K, et al. Roles of glutamate receptor delta 2 subunit (GluRdelta 2) and metabotropic glutamate receptor subtype 1 (mGluR1) in climbing fiber synapse elimination during postnatal cerebellar development. J Neurosci. 2001;21:9701–12. 10.1523/JNEUROSCI.21-24-09701.2001. PubMed PMC

Zuo J, De Jager PL, Takahashi KA, Jiang W, Linden DJ, Heintz N. Neurodegeneration in lurcher mice caused by mutation in delta2 glutamate receptor gene. Nature. 1997;388:769–73. 10.1038/42009. PubMed

Araki K, Meguro H, Kushiya E, Takayama C, Inoue Y, Mishina M. Selective expression of the glutamate receptor channel delta 2 subunit in cerebellar purkinje cells. Biochem Biophys Res Commun. 1993;197:1267–76. 10.1006/bbrc.1993.2614. PubMed

Hepp R, Hay YA, Aguado C, Lujan R, Dauphinot L, Potier MC, et al. Glutamate receptors of the delta family are widely expressed in the adult brain. Brain Struct Funct. 2015;220:2797–815. 10.1007/s00429-014-0827-4. PubMed

Kakegawa W, Miyoshi Y, Hamase K, Matsuda S, Matsuda K, Kohda K, et al. D-serine regulates cerebellar LTD and motor coordination through the delta2 glutamate receptor. Nat Neurosci. 2011;14:603–11. 10.1038/nn.2791. PubMed

Naur P, Hansen KB, Kristensen AS, Dravid SM, Pickering DS, Olsen L, et al. Ionotropic glutamate-like receptor delta2 binds D-serine and glycine. Proc Natl Acad Sci U S A. 2007;104:14116–21. 10.1073/pnas.0703718104. PubMed PMC

Burada AP, Vinnakota R, Kumar J. The architecture of GluD2 ionotropic delta glutamate receptor elucidated by cryo-EM. J Struct Biol. 2020;211:107546. 10.1016/j.jsb.2020.107546. PubMed

Zhao HM, Wenthold RJ, Wang YX, Petralia RS. Delta-glutamate receptors are differentially distributed at parallel and climbing fiber synapses on purkinje cells. J Neurochem. 1997;68:1041–52. 10.1046/j.1471-4159.1997.68031041.x. PubMed

Yuzaki M, Cerebellar. LTD vs. motor learning-lessons learned from studying GluD2. Neural Netw. 2013;47:36–41. 10.1016/j.neunet.2012.07.001. PubMed

Kakegawa W, Miyazaki T, Kohda K, Matsuda K, Emi K, Motohashi J, et al. The N-terminal domain of GluD2 (GluRdelta2) recruits presynaptic terminals and regulates synaptogenesis in the cerebellum in vivo. J Neurosci. 2009;29:5738–48. 10.1523/JNEUROSCI.6013-08.2009. PubMed PMC

Kohda K, Kakegawa W, Yuzaki M. Unlocking the secrets of the delta2 glutamate receptor: A gatekeeper for synaptic plasticity in the cerebellum. Commun Integr Biol. 2013;6:e26466. 10.4161/cib.26466. PubMed PMC

Hirano T. Long-term depression and other synaptic plasticity in the cerebellum. Proc Jpn Acad Ser B Phys Biol Sci. 2013;89:183–95. 10.2183/pjab.89.183. PubMed PMC

Grandes P, Ortega F, Streit P. Glutamate-immunoreactive climbing fibres in the cerebellar cortex of the rat. Histochemistry. 1994;101:427–37. 10.1007/BF00269493. PubMed

Stell BM, Rostaing P, Triller A, Marty A. Activation of presynaptic GABA(A) receptors induces glutamate release from parallel fiber synapses. J Neurosci. 2007;27:9022–31. 10.1523/JNEUROSCI.1954-07.2007. PubMed PMC

Ady V, Perroy J, Tricoire L, Piochon C, Dadak S, Chen X, et al. Type 1 metabotropic glutamate receptors (mGlu1) trigger the gating of GluD2 delta glutamate receptors. EMBO Rep. 2014;15:103–9. 10.1002/embr.201337371. PubMed PMC

Catterall WA, Swanson TM. Structural basis for Pharmacology of Voltage-Gated sodium and calcium channels. Mol Pharmacol. 2015;88:141–50. 10.1124/mol.114.097659. PubMed PMC

Daniel H, Hemart N, Jaillard D, Crepel F. Coactivation of metabotropic glutamate receptors and of voltage-gated calcium channels induces long-term depression in cerebellar purkinje cells in vitro. Exp Brain Res. 1992;90:327–31. 10.1007/BF00227245. PubMed

Hansel C, de Jeu M, Belmeguenai A, Houtman SH, Buitendijk GH, Andreev D, et al. AlphaCaMKII is essential for cerebellar LTD and motor learning. Neuron. 2006;51:835–43. 10.1016/j.neuron.2006.08.013. PubMed

Antunes G, Roque AC, Simoes-de-Souza FM. Stochastic induction of Long-Term potentiation and Long-Term depression. Sci Rep. 2016;6:30899. 10.1038/srep30899. PubMed PMC

Salzano M, Rusciano MR, Russo E, Bifulco M, Postiglione L, Vitale M. Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates Raf-1 at Serine 338 and mediates Ras-stimulated Raf-1 activation. Cell Cycle. 2012;11:2100–6. 10.4161/cc.20543. PubMed

Illario M, Cavallo AL, Bayer KU, Di Matola T, Fenzi G, Rossi G, et al. Calcium/calmodulin-dependent protein kinase II binds to Raf-1 and modulates integrin-stimulated ERK activation. J Biol Chem. 2003;278:45101–8. 10.1074/jbc.M305355200. PubMed

Yawata S, Tsuchida H, Kengaku M, Hirano T. Membrane-proximal region of glutamate receptor delta2 subunit is critical for long-term depression and interaction with protein interacting with C kinase 1 in a cerebellar purkinje neuron. J Neurosci. 2006;26:3626–33. 10.1523/JNEUROSCI.4183-05.2006. PubMed PMC

Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron. 2000;28:499–510. 10.1016/s0896-6273(00)00128-8. PubMed

Lu W, Ziff EB. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron. 2005;47:407–21. 10.1016/j.neuron.2005.07.006. PubMed

Ito M. Long-term depression. Annu Rev Neurosci. 1989;12:85–102. 10.1146/annurev.ne.12.030189.000505. PubMed

Ito M, Sakurai M, Tongroach P. Climbing fibre induced depression of both mossy fibre responsiveness and glutamate sensitivity of cerebellar purkinje cells. J Physiol. 1982;324:113–34. 10.1113/jphysiol.1982.sp014103. PubMed PMC

Hansel C, Linden DJ. Long-term depression of the cerebellar climbing fiber–Purkinje neuron synapse. Neuron. 2000;26:473–82. 10.1016/s0896-6273(00)81179-4. PubMed

Ohtsuki G, Piochon C, Hansel C. Climbing fiber signaling and cerebellar gain control. Front Cell Neurosci. 2009;3:4. 10.3389/neuro.03.004.2009. PubMed PMC

Steuber V, Mittmann W, Hoebeek FE, Silver RA, De Zeeuw CI, Hausser M, et al. Cerebellar LTD and pattern recognition by purkinje cells. Neuron. 2007;54:121–36. 10.1016/j.neuron.2007.03.015. PubMed PMC

Strata P, Rossi F. Plasticity of the olivocerebellar pathway. Trends Neurosci. 1998;21:407–13. 10.1016/s0166-2236(98)01305-8. PubMed

Kano M, Watanabe T, Uesaka N, Watanabe M. Multiple phases of climbing Fiber synapse elimination in the developing cerebellum. Cerebellum. 2018;17:722–34. 10.1007/s12311-018-0964-z. PubMed

Crepel F, Delhaye-Bouchaud N, Dupont JL. Fate of the multiple innervation of cerebellar purkinje cells by climbing fibers in immature control, x-irradiated and hypothyroid rats. Brain Res. 1981;227:59–71. doi 10.1016/0165–3806(81)90094-8. PubMed

Mariani J, Changeux JP. Ontogenesis of olivocerebellar relationships. I. Studies by intracellular recordings of the multiple innervation of purkinje cells by climbing fibers in the developing rat cerebellum. J Neurosci. 1981;1:696–702. 10.1523/JNEUROSCI.01-07-00696.1981. PubMed PMC

Kurihara H, Hashimoto K, Kano M, Takayama C, Sakimura K, Mishina M, et al. Impaired parallel fiber–>Purkinje cell synapse stabilization during cerebellar development of mutant mice lacking the glutamate receptor delta2 subunit. J Neurosci. 1997;17:9613–23. 10.1523/JNEUROSCI.17-24-09613.1997. PubMed PMC

Kano M, Hashimoto K, Chen C, Abeliovich A, Aiba A, Kurihara H, et al. Impaired synapse elimination during cerebellar development in PKC gamma mutant mice. Cell. 1995;83:1223–31. 10.1016/0092-8674(95)90147-7. PubMed

Kano M, Hashimoto K, Kurihara H, Watanabe M, Inoue Y, Aiba A, et al. Persistent multiple climbing fiber innervation of cerebellar purkinje cells in mice lacking mGluR1. Neuron. 1997;18:71–9. 10.1016/s0896-6273(01)80047-7. PubMed

Offermanns S, Hashimoto K, Watanabe M, Sun W, Kurihara H, Thompson RF, et al. Impaired motor coordination and persistent multiple climbing fiber innervation of cerebellar purkinje cells in mice lacking Galphaq. Proc Natl Acad Sci U S A. 1997;94:14089–94. 10.1073/pnas.94.25.14089. PubMed PMC

Hashimoto K, Watanabe M, Kurihara H, Offermanns S, Jiang H, Wu Y, et al. Climbing fiber synapse elimination during postnatal cerebellar development requires signal transduction involving G alpha Q and phospholipase C beta 4. Prog Brain Res. 2000;124:31–48. 10.1016/S0079-6123(00)24006-5. PubMed

Hashimoto K, Kano M. Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum. Neuron. 2003;38:785–96. 10.1016/s0896-6273(03)00298-8. PubMed

Hirano T. Glutamate-receptor-like molecule GluRdelta2 involved in synapse formation at parallel fiber-Purkinje neuron synapses. Cerebellum. 2012;11:71–7. 10.1007/s12311-010-0170-0. PubMed

Ichikawa R, Miyazaki T, Kano M, Hashikawa T, Tatsumi H, Sakimura K, et al. Distal extension of climbing fiber territory and multiple innervation caused by aberrant wiring to adjacent spiny branchlets in cerebellar purkinje cells lacking glutamate receptor delta 2. J Neurosci. 2002;22:8487–503. 10.1523/JNEUROSCI.22-19-08487.2002. PubMed PMC

Rabacchi SA, Bailly Y, Delhaye-Bouchaud N, Herrup K, Mariani J. Role of the target in synapse elimination: studies in cerebellum of developing lurcher mutants and adult chimeric mice. J Neurosci. 1992;12:4712–20. 10.1523/JNEUROSCI.12-12-04712.1992. PubMed PMC

Kohda K, Kakegawa W, Matsuda S, Nakagami R, Kakiya N, Yuzaki M. The extreme C-terminus of GluRdelta2 is essential for induction of long-term depression in cerebellar slices. Eur J Neurosci. 2007;25:1357–62. 10.1111/j.1460-9568.2007.05412.x. PubMed

Morando L, Cesa R, Rasetti R, Harvey R, Strata P. Role of glutamate delta– 2 receptors in activity-dependent competition between heterologous afferent fibers. Proc Natl Acad Sci U S A. 2001;98:9954–9. 10.1073/pnas.171098398. PubMed PMC

Carrillo E, Gonzalez CU, Berka V, Jayaraman V. Delta glutamate receptors are functional glycine- and -serine-gated cation channels in situ. Sci Adv. 2021;7:eabk2200. 10.1126/sciadv.abk2200. PubMed PMC

Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, et al. Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nat Neurosci. 2005;8:1534–41. 10.1038/nn1576. PubMed

Uchigashima M, Cheung A, Suh J, Watanabe M, Futai K. Differential expression of neurexin genes in the mouse brain. J Comp Neurol. 2019;527:1940–65. 10.1002/cne.24664. PubMed PMC

Ito-Ishida A, Miura E, Emi K, Matsuda K, Iijima T, Kondo T, et al. Cbln1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar purkinje cells in vitro and in vivo. J Neurosci. 2008;28:5920–30. 10.1523/JNEUROSCI.1030-08.2008. PubMed PMC

Takeo YH, Shuster SA, Jiang L, Hu MC, Luginbuhl DJ, Rulicke T et al. GluD2- and Cbln1-mediated competitive interactions shape the dendritic arbors of cerebellar Purkinje cells. Neuron. 2021;109:629– 44 e8. 10.1016/j.neuron.2020.11.028 PubMed PMC

Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, et al. Trans-synaptic interaction of GluRdelta2 and neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell. 2010;141:1068–79. 10.1016/j.cell.2010.04.035. PubMed

Nakamoto C, Konno K, Miyazaki T, Nakatsukasa E, Natsume R, Abe M, et al. Expression mapping, quantification, and complex formation of GluD1 and GluD2 glutamate receptors in adult mouse brain. J Comp Neurol. 2020;528:1003–27. 10.1002/cne.24792. PubMed

Caddy KW, Biscoe TJ. Structural and quantitative studies on the normal C3H and lurcher mutant mouse. Philos Trans R Soc Lond B Biol Sci. 1979;287:167–201. PubMed

Kolinko Y, Cendelin J, Kralickova M, Tonar Z. Smaller absolute quantities but greater relative densities of microvessels are associated with cerebellar degeneration in lurcher mice. Front Neuroanat. 2016;10:35. 10.3389/fnana.2016.00035. PubMed PMC

Caddy KW, Herrup K. The fine structure of the purkinje cell and its afferents in lurcher chimeric mice. J Comp Neurol. 1991;305:421–34. 10.1002/cne.903050306. PubMed

Zanjani SH, Selimi F, Vogel MW, Haeberle AM, Boeuf J, Mariani J, et al. Survival of interneurons and parallel fiber synapses in a cerebellar cortex deprived of purkinje cells: studies in the double mutant mouse Grid2Lc/+;Bax(-/-). J Comp Neurol. 2006;497:622–35. 10.1002/cne.21017. PubMed

Dumesnil-Bousez N, Sotelo C. Early development of the lurcher cerebellum: purkinje cell alterations and impairment of synaptogenesis. J Neurocytol. 1992;21:506–29. PubMed

Selimi F, Doughty M, Delhaye-Bouchaud N, Mariani J. Target-related and intrinsic neuronal death in lurcher mutant mice are both mediated by caspase-3 activation. J Neurosci. 2000;20:992–1000. PubMed PMC

Vogel MW, Caston J, Yuzaki M, Mariani J. The lurcher mouse: fresh insights from an old mutant. Brain Res. 2007;1140:4–18. 10.1016/j.brainres.2005.11.086. PubMed

Wullner U, Loschmann PA, Weller M, Klockgether T. Apoptotic cell death in the cerebellum of mutant weaver and lurcher mice. Neurosci Lett. 1995;200:109–12. doi 10.1016/0304–3940(95)12090-q. PubMed

Yue Z, Horton A, Bravin M, DeJager PL, Selimi F, Heintz N. A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice. Neuron. 2002;35:921–33. PubMed

Chu T, Hullinger H, Schilling K, Oberdick J. Spatial and Temporal changes in natural and target deprivation-induced cell death in the mouse inferior Olive. J Neurobiol. 2000;43:18–30. doi 10.1002/(sici)1097–4695(200004)43:1 < 18::aid-neu2 > 3.0.co;2-c. PubMed

Wetts R, Herrup K. Interaction of granule, purkinje and inferior olivary neurons in lurcher chimeric mice. II. Granule cell death. Brain Res. 1982;250:358–62. PubMed

Wetts R, Herrup K. Interaction of granule, purkinje and inferior olivary neurons in lurcher chimaeric mice. I. Qualitative studies. J Embryol Exp Morphol. 1982;68:87–98. PubMed

De Jager PL, Zuo J, Cook SA, Heintz N. A new allele of the lurcher gene, lurcherj. Mamm Genome. 1997;8:647–50. PubMed

Zanjani HS, McFarland R, Cavelier P, Blokhin A, Gautheron V, Levenes C, et al. Death and survival of heterozygous lurcher purkinje cells in vitro. Dev Neurobiol. 2009;69:505–17. 10.1002/dneu.20715. PubMed PMC

Armstrong CL, Duffin CA, McFarland R, Vogel MW. Mechanisms of compartmental purkinje cell death and survival in the lurcher mutant mouse. Cerebellum. 2011;10:504–14. 10.1007/s12311-010-0231-4. PubMed

Choi K, Kim J, Kim GW, Choi C. Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species. Curr Neurovasc Res. 2009;6:213–22. 10.2174/156720209789630375. PubMed

Goll DE, Thompson VF, Li H, Wei W, Cong J. The Calpain system. Physiol Rev. 2003;83:731–801. 10.1152/physrev.00029.2002. PubMed

Polster BM, Basanez G, Etxebarria A, Hardwick JM, Nicholls DG. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem. 2005;280:6447–54. 10.1074/jbc.M413269200. PubMed

Lopatniuk P, Witkowski JM. Conventional calpains and programmed cell death. Acta Biochim Pol. 2011;58:287–96. PubMed

Norberg E, Gogvadze V, Ott M, Horn M, Uhlen P, Orrenius S, et al. An increase in intracellular Ca2 + is required for the activation of mitochondrial Calpain to release AIF during cell death. Cell Death Differ. 2008;15:1857–64. 10.1038/cdd.2008.123. PubMed

Cabon L, Galan-Malo P, Bouharrour A, Delavallee L, Brunelle-Navas MN, Lorenzo HK, et al. BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation. Cell Death Differ. 2012;19:245–56. 10.1038/cdd.2011.91. PubMed PMC

Gil-Parrado S, Fernandez-Montalvan A, Assfalg-Machleidt I, Popp O, Bestvater F, Holloschi A, et al. Ionomycin-activated Calpain triggers apoptosis. A probable role for Bcl-2 family members. J Biol Chem. 2002;277:27217–26. 10.1074/jbc.M202945200. PubMed

Gao G, Dou QP. N-terminal cleavage of Bax by Calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death. J Cell Biochem. 2000;80:53–72. 10.1002/1097-4644(20010101)80:153:aid-jcb603.0.co2-e. PubMed DOI

Wolf BB, Schuler M, Echeverri F, Green DR. Caspase-3 is the primary activator of apoptotic DNA fragmentation via DNA fragmentation factor-45/inhibitor of caspase-activated DNase inactivation. J Biol Chem. 1999;274:30651–6. 10.1074/jbc.274.43.30651. PubMed

Frischmuth S, Kranda K, Baurle J. Translocation of cytochrome C during cerebellar degeneration in lurcher and weaver mutant mice. Brain Res Bull. 2006;71:139–48. 10.1016/j.brainresbull.2006.08.012. PubMed

Nishiyama J, Yuzaki M. Excitotoxicity and autophagy: lurcher May not be a model of autophagic cell death. Autophagy. 2010;6:568–70. 10.4161/auto.6.4.11951. PubMed

Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011;13:132–41. 10.1038/ncb2152. PubMed PMC

Das S, Dutta P, Mazumder M, Seal S, Duraivelan K, Samanta D et al. nPIST: A novel actin binding protein of trans-Golgi network. bioRxiv. 2018:270363. 10.1101/270363

Liang XH, Jackson S, Seaman M, Brown K, Kempkes B, Hibshoosh H, et al. Induction of autophagy and Inhibition of tumorigenesis by Beclin 1. Nature. 1999;402:672–6. 10.1038/45257. PubMed

Liang XH, Kleeman LK, Jiang HH, Gordon G, Goldman JE, Berry G, et al. Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J Virol. 1998;72:8586–96. 10.1128/JVI.72.11.8586-8596.1998. PubMed PMC

Wang QJ, Ding Y, Kohtz DS, Mizushima N, Cristea IM, Rout MP, et al. Induction of autophagy in axonal dystrophy and degeneration. J Neurosci. 2006;26:8057–68. 10.1523/jneurosci.2261-06.2006. PubMed PMC

Nishiyama J, Matsuda K, Kakegawa W, Yamada N, Motohashi J, Mizushima N, et al. Reevaluation of neurodegeneration in lurcher mice: constitutive ion fluxes cause cell death with, not by, autophagy. J Neurosci. 2010;30:2177–87. doi 10.1523/JNEUROSCI.6030– 09.2010. PubMed PMC

Zhu L, Ramboz S, Hewitt D, Boring L, Grass DS, Purchio AF. Non-invasive imaging of GFAP expression after neuronal damage in mice. Neurosci Lett. 2004;367:210–2. 10.1016/j.neulet.2004.06.020. PubMed

Schulze-Osthoff K, Ferrari D, Los M, Wesselborg S, Peter ME. Apoptosis signaling by death receptors. Eur J Biochem. 1998;254:439–59. 10.1046/j.1432-1327.1998.2540439.x. PubMed

Choi C, Benveniste EN. Fas Ligand/Fas system in the brain: regulator of immune and apoptotic responses. Brain Res Brain Res Rev. 2004;44:65–81. 10.1016/j.brainresrev.2003.08.007. PubMed

Letellier E, Kumar S, Sancho-Martinez I, Krauth S, Funke-Kaiser A, Laudenklos S, et al. CD95-ligand on peripheral myeloid cells activates Syk kinase to trigger their recruitment to the inflammatory site. Immunity. 2010;32:240–52. 10.1016/j.immuni.2010.01.011. PubMed

Salomova M, Tichanek F, Jelinkova D, Cendelin J. Abnormalities in the cerebellar levels of trophic factors BDNF and GDNF in Pcd and lurcher cerebellar mutant mice. Neurosci Lett. 2020;725:134870. 10.1016/j.neulet.2020.134870. PubMed

Vernet-der Garabedian B, Derer P, Bailly Y, Mariani J. Innate immunity in the Grid2Lc/+ mouse model of cerebellar neurodegeneration: glial CD95/CD95L plays a non-apoptotic role in persistent neuron loss-associated inflammatory reactions in the cerebellum. J Neuroinflammation. 2013;10:65. 10.1186/1742-2094-10-65. PubMed PMC

Reader TA, Strazielle C, Botez MI, Lalonde R. Brain dopamine and amino acid concentrations in lurcher mutant mice. Brain Res Bull. 1998;45:489–93. PubMed

Strazielle C, Lalonde R, Riopel L, Botez MI, Reader TA. Regional distribution of the 5-HT innervation in the brain of normal and lurcher mice as revealed by [3H]citalopram quantitative autoradiography. J Chem Neuroanat. 1996;10:157–71. doi 10.1016/0891– 0618(96)00115-9. PubMed

Heckroth JA. Quantitative morphological analysis of the cerebellar nuclei in normal and lurcher mutant mice. I. Morphology and cell number. J Comp Neurol. 1994;343:173–82. 10.1002/cne.903430113. PubMed

Ito M, Yoshida M. The origin of cerebral-induced Inhibition of deiters neurones. I. Monosynaptic initiation of the inhibitory postsynaptic potentials. Exp Brain Res. 1966;2:330–49. 10.1007/BF00234779. PubMed

Linnemann C, Sultan F, Pedroarena CM, Schwarz C, Thier P. Lurcher mice exhibit potentiation of GABA(A)-receptor-mediated conductance in cerebellar nuclei neurons in close Temporal relationship to purkinje cell death. J Neurophysiol. 2004;91:1102–7. 10.1152/jn.00163.2003. PubMed

Sultan F, Konig T, Mock M, Thier P. Quantitative organization of neurotransmitters in the deep cerebellar nuclei of the lurcher mutant. J Comp Neurol. 2002;452:311–23. 10.1002/cne.10365. PubMed

Gallo V, Ciotti MT, Coletti A, Aloisi F, Levi G. Selective release of glutamate from cerebellar granule cells differentiating in culture. Proc Natl Acad Sci U S A. 1982;79:7919–23. 10.1073/pnas.79.24.7919. PubMed PMC

Perciavalle V, Berretta S, Raffaele R. Projections from the intracerebellar nuclei to the ventral midbrain tegmentum in the rat. Neuroscience. 1989;29:109–19. doi 10.1016/0306–4522(89)90336-9. PubMed

Snider RS, Maiti A, Snider SR. Cerebellar pathways to ventral midbrain and Nigra. Exp Neurol. 1976;53:714–28. 10.1016/0014-4886(76)90150-3. PubMed

Babuska V, Houdek Z, Tuma J, Purkartova Z, Tumova J, Kralickova M, et al. Transplantation of embryonic cerebellar grafts improves gait parameters in ataxic lurcher mice. Cerebellum. 2015;14:632–41. 10.1007/s12311-015-0656-x. PubMed

Salomova M, Tichanek F, Jelinkova D, Cendelin J. Forced activity and environmental enrichment mildly improve manifestation of rapid cerebellar degeneration in mice. Behav Brain Res. 2021;401:113060. 10.1016/j.bbr.2020.113060. PubMed

Vernet-der Garabedian B, Lemaigre-Dubreuil Y, Delhaye-Bouchaud N, Mariani J. Abnormal IL-1beta cytokine expression in the cerebellum of the ataxic mutant mice staggerer and lurcher. Brain Res Mol Brain Res. 1998;62:224–7. PubMed

Bakalian A, Kopmels B, Messer A, Fradelizi D, Delhaye-Bouchaud N, Wollman E, et al. Peripheral macrophage abnormalities in mutant mice with spinocerebellar degeneration. Res Immunol. 1992;143:129–39. PubMed

Mandáková P, Virtová M, Síma P, Beranová M, Slípka J. Congenitally determined neurodegeneration lurcher induces morphofunctional changes of thymus. Folia Microbiol (Praha). 2003;48:394–8. 10.1007/bf02931373. PubMed

Fortier PA, Smith AM, Rossignol S. Locomotor deficits in the mutant mouse, lurcher. Exp Brain Res. 1987;66:271–86. PubMed

Cendelin J, Voller J, Vozeh F. Ataxic gait analysis in a mouse model of the olivocerebellar degeneration. Behav Brain Res. 2010;210:8–15. 10.1016/j.bbr.2010.01.035. PubMed

Strazielle C, Lalonde R. Grooming in lurcher mutant mice. Physiol Behav. 1998;64:57–61. PubMed

Lalonde R, Lamarre Y, Smith AM, Botez MI. Spontaneous alternation and habituation in lurcher mutant mice. Brain Res. 1986;362:161–4. PubMed

Lalonde R, Joyal CC, Thifault S. Beam sensorimotor learning and habituation to motor activity in lurcher mutant mice. Behav Brain Res. 1996;74:213–6. PubMed

Hartmann N, Martrette JM, Westphal A. Influence of the lurcher mutation on myosin heavy chain expression in skeletal and cardiac muscles. J Cell Biochem Suppl. 2001;Suppl 36:222–31. 10.1002/jcb.1109. PubMed

Jindrová A, Tuma J, Sládek V. Impact of Non-Invasively induced motor deficits on tibial cortical properties in mutant lurcher mice. PLoS ONE. 2016;11:e0158877. 10.1371/journal.pone.0158877. PubMed PMC

Cox RH, Hubbard JW, Lawler JE, Sanders BJ, Mitchell VP. Cardiovascular and sympathoadrenal responses to stress in swim-trained rats. J Appl Physiol (1985). 1985;58:1207–14. 10.1152/jappl.1985.58.4.1207. PubMed

Radmard S, Zesiewicz TA, Kuo SH. Evaluation of cerebellar ataxic patients. Neurol Clin. 2023;41:21–44. 10.1016/j.ncl.2022.05.002. PubMed PMC

Zhou H, Nguyen H, Enriquez A, Morsy L, Curtis M, Piser T, et al. Assessment of gait and balance impairment in people with spinocerebellar ataxia using wearable sensors. Neurol Sci. 2022;43:2589–99. 10.1007/s10072-021-05657-6. PubMed

Manto M, Serrao M, Filippo Castiglia S, Timmann D, Tzvi-Minker E, Pan MK, et al. Neurophysiology of cerebellar ataxias and gait disorders. Clin Neurophysiol Pract. 2023;8:143–60. 10.1016/j.cnp.2023.07.002. PubMed PMC

Ilg W, Milne S, Schmitz-Hubsch T, Alcock L, Beichert L, Bertini E, et al. Quantitative gait and balance outcomes for Ataxia trials: consensus recommendations by the Ataxia global initiative working group on Digital-Motor biomarkers. Cerebellum. 2024;23:1566–92. 10.1007/s12311-023-01625-2. PubMed PMC

Diener HC, Dichgans J. Pathophysiology of cerebellar ataxia. Mov Disord. 1992;7:95–109. 10.1002/mds.870070202. PubMed

Serrao M, Ranavolo A, Casali C. Neurophysiology of gait. Handb Clin Neurol. 2018;154:299–303. 10.1016/B978-0-444-63956-1.00018. PubMed DOI

Velazquez-Perez L, Rodriguez-Diaz JC, Rodriguez-Labrada R, Medrano-Montero J, Aguilera Cruz AB, Reynaldo-Cejas L, et al. Neurorehabilitation improves the motor features in prodromal SCA2: A randomized, controlled trial. Mov Disord. 2019;34:1060–8. 10.1002/mds.27676. PubMed

Gudlavalleti A, Tenny S, Cerebellar Neurological S. 2022 Oct 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 32310540. PubMed

Ataullah AHM, Singla R, Naqvi IA, Cerebellar D. 2024 May 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 32965988.

Dunham NW, Miya TS. A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc. 1957;46:208–9. 10.1002/jps.3030460322. PubMed

Hilber P, Caston J. Motor skills and motor learning in lurcher mutant mice during aging. Neuroscience. 2001;102:615–23. PubMed

Le Marec N, Lalonde R. Treadmill performance of mice with cerebellar lesions: 2. Lurcher mutant mice. Neurobiol Learn Mem. 2000;73:195–206. 10.1006/nlme.1999.3926. PubMed

Thullier F, Lalonde R, Cousin X, Lestienne F. Neurobehavioral evaluation of lurcher mutant mice during ontogeny. Brain Res Dev Brain Res. 1997;100:22–8. PubMed

Castro B, Kuang S. Evaluation of muscle performance in mice by treadmill exhaustion test and Whole-limb grip strength assay. Bio Protoc. 2017;7. 10.21769/BioProtoc.2237. PubMed PMC

Serradj N, Jamon M. Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j. Behav Brain Res. 2007;177:80–9. 10.1016/j.bbr.2006.11.001. PubMed

Winser SJ, Chan AYY, Chung R, Whitney S, Kannan P. Validity of balance measures in cerebellar ataxia: A prospective study with 12-month follow-up. PM R. 2023;15:742–50. 10.1002/pmrj.12826. PubMed

Forbes J, Munakomi S, Cronovich HA, Romberg T. 2023 Aug 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 33085334. PubMed

Kashyap B, Phan D, Pathirana PN, Horne M, Power L, Szmulewicz D. Objective assessment of cerebellar ataxia: A comprehensive and refined approach. Sci Rep. 2020;10:9493. 10.1038/s41598-020-65303-7. PubMed PMC

Marquer A, Barbieri G, Perennou D. The assessment and treatment of postural disorders in cerebellar ataxia: a systematic review. Ann Phys Rehabil Med. 2014;57:67–78. 10.1016/j.rehab.2014.01.002. PubMed

Hilber P, Lalonde R, Caston J. An unsteady platform test for measuring static equilibrium in mice. J Neurosci Methods. 1999;88:201–5. PubMed

Jacobi H, Alfes J, Minnerop M, Konczak J, Klockgether T, Timmann D. Dual task effect on postural control in patients with degenerative cerebellar disorders. Cerebellum Ataxias. 2015;2:6. 10.1186/s40673-015-0025-z. PubMed PMC

Liu XH, Li Y, Xu HL, Sikandar A, Lin WH, Li GH, et al. Quantitative assessment of postural instability in spinocerebellar ataxia type 3 patients. Ann Clin Transl Neurol. 2020;7:1360–70. 10.1002/acn3.51124. PubMed PMC

Pommerening H, van Dullemen S, Kieslich M, Schubert R, Zielen S, Voss S. Body composition, muscle strength and hormonal status in patients with ataxia telangiectasia: a cohort study. Orphanet J Rare Dis. 2015;10:155. 10.1186/s13023-015-0373-z. PubMed PMC

Pullen RL. Jr. Neurologic assessment for pronator drift. Nursing. 2004;34:22. 10.1097/00152193-200403000-00019. PubMed

Krizkova A, Vozeh F. Development of early motor learning and topical motor skills in a model of cerebellar degeneration. Behav Brain Res. 2004;150:65–72. 10.1016/S0166-4328(03)00247-X. PubMed

Lalonde R, Botez MI, Joyal CC, Caumartin M. Motor abnormalities in lurcher mutant mice. Physiol Behav. 1992;51:523–5. 10.1016/0031-9384(92)90174-Z. PubMed

Lalonde R, Filali M, Bensoula AN, Lestienne F. Sensorimotor learning in three cerebellar mutant mice. Neurobiol Learn Mem. 1996;65:113–20. 10.1006/nlme.1996.0013. PubMed

Strazielle C, Kremarik P, Ghersi-Egea JF, Lalonde R. Regional brain variations of cytochrome oxidase activity and motor coordination in lurcher mutant mice. Exp Brain Res. 1998;121:35–45. PubMed

Hilber P, Lorivel T, Delarue C, Caston J. Stress and anxious-related behaviors in lurcher mutant mice. Brain Res. 2004;1003:108–12. 10.1016/j.brainres.2004.01.008. PubMed

Lalonde R. Motor learning in lurcher mutant mice. Brain Res. 1994;639:351–3. PubMed

Lalonde R, Bensoula AN, Filali M. Rotorod sensorimotor learning in cerebellar mutant mice. Neurosci Res. 1995;22:423–6. 10.1016/0168-0102(95)00916-H. PubMed

Le Marec N, Caston J, Lalonde R. Impaired motor skills on static and mobile beams in lurcher mutant mice. Exp Brain Res. 1997;116:131–8. PubMed

Caston J, Vasseur F, Stelz T, Chianale C, Delhaye-Bouchaud N, Mariani J. Differential roles of cerebellar cortex and deep cerebellar nuclei in the learning of the equilibrium behavior: studies in intact and cerebellectomized lurcher mutant mice. Brain Res Dev Brain Res. 1995;86:311–6. PubMed

Heckroth JA. A quantitative morphological analysis of the cerebellar nuclei in normal and lurcher mutant mice. II. Volumetric changes in cytological components. J Comp Neurol. 1994;343:183–92. 10.1002/cne.903430114. PubMed

Rondi-Reig L, Paradis AL, Lefort JM, Babayan BM, Tobin C. How the cerebellum May monitor sensory information for Spatial representation. Front Syst Neurosci. 2014;8:205. 10.3389/fnsys.2014.00205. PubMed PMC

Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex. 2010;46:845–57. 10.1016/j.cortex.2009.06.009. PubMed

Kamali A, Milosavljevic S, Gandhi A, Lano KR, Shobeiri P, Sherbaf FG, et al. The Cortico-Limbo-Thalamo-Cortical circuits: an update to the original Papez circuit of the human limbic system. Brain Topogr. 2023;36:371–89. 10.1007/s10548-023-00955-y. PubMed PMC

Shipman ML, Green JT. Cerebellum and cognition: does the rodent cerebellum participate in cognitive functions? Neurobiol Learn Mem. 2019;106996. 10.1016/j.nlm.2019.02.006. PubMed

Cendelin J, Korelusova I, Vozeh F. The effect of repeated Rotarod training on motor skills and Spatial learning ability in lurcher mutant mice. Behav Brain Res. 2008;189:65–74. 10.1016/j.bbr.2007.12.013. PubMed

Cendelin J. From mice to men: lessons from mutant ataxic mice. Cerebellum Ataxias. 2014;1:4. 10.1186/2053-8871-1-4. PubMed PMC

Hilber P, Jouen F, Delhaye-Bouchaud N, Mariani J, Caston J. Differential roles of cerebellar cortex and deep cerebellar nuclei in learning and retention of a Spatial task: studies in intact and cerebellectomized lurcher mutant mice. Behav Genet. 1998;28:299–308. PubMed

Lalonde R, Lamarre Y, Smith AM. Does the mutant mouse lurcher have deficits in spatially oriented behaviours? Brain Res. 1988;455:24–30. PubMed

Lalonde R, Thifault S. Absence of an association between motor coordination and Spatial orientation in lurcher mutant mice. Behav Genet. 1994;24:497–501. PubMed

Porras-Garcia E, Cendelin J, Dominguez-del-Toro E, Vozeh F, Delgado-Garcia JM. Purkinje cell loss affects differentially the execution, acquisition and prepulse Inhibition of skeletal and facial motor responses in lurcher mice. Eur J Neurosci. 2005;21:979–88. 10.1111/j.1460-9568.2005.03940.x. PubMed

Belzung C, Chapillon P, Lalonde R. The effects of the lurcher mutation on object localization, T-maze discrimination, and radial arm maze tasks. Behav Genet. 2001;31:151–5. PubMed

Lalonde R, Filali M, Bensoula AN, Monnier C, Guastavino JM. Spatial learning in a Z-maze by cerebellar mutant mice. Physiol Behav. 1996;59:83–6. PubMed

d’Isa R, Comi G, Leocani L. Apparatus design and behavioural testing protocol for the evaluation of Spatial working memory in mice through the spontaneous alternation T-maze. Sci Rep. 2021;11:21177. 10.1038/s41598-021-00402-7. PubMed PMC

Wallesch CW, Horn A. Long-term effects of cerebellar pathology on cognitive functions. Brain Cogn. 1990;14:19–25. doi 10.1016/0278–2626(90)90057-u. PubMed

Dickson PE, Rogers TD, Del Mar N, Martin LA, Heck D, Blaha CD, et al. Behavioral flexibility in a mouse model of developmental cerebellar purkinje cell loss. Neurobiol Learn Mem. 2010;94:220–8. 10.1016/j.nlm.2010.05.010. PubMed PMC

Lorivel T, Roy V, Hilber P. Fear-related behaviors in lurcher mutant mice exposed to a predator. Genes Brain Behav. 2014;13:794–801. 10.1111/gbb.12173. PubMed

Monnier C, Lalonde R. Elevated (+)-maze and hole-board exploration in lurcher mutant mice. Brain Res. 1995;702:169–72. PubMed

Leroi I, O’Hearn E, Marsh L, Lyketsos CG, Rosenblatt A, Ross CA, et al. Psychopathology in patients with degenerative cerebellar diseases: a comparison to Huntington’s disease. Am J Psychiatry. 2002;159:1306–14. 10.1176/appi.ajp.159.8.1306. PubMed

Caston J, Chianale C, Delhaye-Bouchaud N, Mariani J. Role of the cerebellum in exploration behavior. Brain Res. 1998;808:232–7. PubMed

Tuma J, Kolinko Y, Vozeh F, Cendelin J. Mutation-related differences in exploratory, Spatial, and depressive-like behavior in Pcd and lurcher cerebellar mutant mice. Front Behav Neurosci. 2015;9:116. 10.3389/fnbeh.2015.00116. PubMed PMC

Lefort JM, Vincent J, Tallot L, Jarlier F, De Zeeuw CI, Rondi-Reig L, et al. Impaired cerebellar purkinje cell potentiation generates unstable Spatial map orientation and inaccurate navigation. Nat Commun. 2019;10:2251. 10.1038/s41467-019-09958-5. PubMed PMC

Rochefort C, Arabo A, Andre M, Poucet B, Save E, Rondi-Reig L. Cerebellum shapes hippocampal Spatial code. Science. 2011;334:385–9. 10.1126/science.1207403. PubMed

Lalonde R, Strazielle C. Spontaneous and induced mouse mutations with cerebellar dysfunctions: behavior and neurochemistry. Brain Res. 2007;1140:51–74. 10.1016/j.brainres.2006.01.031. PubMed

Nowak M, Sigmund K. A strategy of win-stay, lose-shift that outperforms tit-for-tat in the prisoner’s dilemma game. Nature. 1993;364:56–8. 10.1038/364056a0. PubMed

Othman MZ, Hassan Z, Che Has AT. Morris water maze: a versatile and pertinent tool for assessing Spatial learning and memory. Exp Anim. 2022;71:264–80. 10.1538/expanim.21-0120. PubMed DOI PMC

Tuma J, Kolinko Y, Jelinkova D, Hilber P, Cendelin J. Impaired Spatial performance in cerebellar-deficient lurcher mice is not associated with their abnormal stress response. Neurobiol Learn Mem. 2017;140:62–70. 10.1016/j.nlm.2017.02.009. PubMed

Vorhees CV, Williams MT. Morris water maze: procedures for assessing Spatial and related forms of learning and memory. Nat Protoc. 2006;1:848–58. 10.1038/nprot.2006.116. PubMed PMC

Martin LA, Goldowitz D, Mittleman G. The cerebellum and Spatial ability: dissection of motor and cognitive components with a mouse model system. Eur J Neurosci. 2003;18:2002–10. 10.1046/j.1460-9568.2003.02921.x. PubMed

de Zeeuw CI, van Alphen AM, Koekkoek SK, Buharin E, Coesmans MP, Morpurgo MM, et al. Recording eye movements in mice: a new approach to investigate the molecular basis of cerebellar control of motor learning and motor timing. Otolaryngol Head Neck Surg. 1998;119:193–203. 10.1016/S0194-5998(98)70054-3. PubMed

Lalonde R, Joyal CC, Cote C, Botez MI. Simultaneous visual discrimination learning in lurcher mutant mice. Brain Res. 1993;618:19–22. PubMed

Harrison FE, Hosseini AH, McDonald MP. Endogenous anxiety and stress responses in water maze and Barnes maze Spatial memory tasks. Behav Brain Res. 2009;198:247–51. 10.1016/j.bbr.2008.10.015. PubMed PMC

Kavushansky A, Richter-Levin G. Effects of stress and corticosterone on activity and plasticity in the amygdala. J Neurosci Res. 2006;84:1580–7. 10.1002/jnr.21058. PubMed

Pavlides C, Nivon LG, McEwen BS. Effects of chronic stress on hippocampal long-term potentiation. Hippocampus. 2002;12:245–57. 10.1002/hipo.1116. PubMed

Cendelin J, Tichanek F. Cerebellar degeneration averts blindness-induced despaired behavior during Spatial task in mice. Neurosci Lett. 2020;722:134854. 10.1016/j.neulet.2020.134854. PubMed

Clausi S, De Luca M, Chiricozzi FR, Tedesco AM, Casali C, Molinari M, et al. Oculomotor deficits affect neuropsychological performance in oculomotor apraxia type 2. Cortex. 2013;49:691–701. 10.1016/j.cortex.2012.02.007. PubMed

Le Ber I, Bouslam N, Rivaud-Pechoux S, Guimaraes J, Benomar A, Chamayou C, et al. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain. 2004;127:759–67. 10.1093/brain/awh080. PubMed

Van Der Giessen RS, Koekkoek SK, van Dorp S, De Gruijl JR, Cupido A, Khosrovani S, et al. Role of olivary electrical coupling in cerebellar motor learning. Neuron. 2008;58:599–612. 10.1016/j.neuron.2008.03.016. PubMed

Velarde MG, Nekorkin VI, Makarov VA, Makarenko VI, Llinas RR. Clustering behavior in a three-layer system mimicking olivo-cerebellar dynamics. Neural Netw. 2004;17:191–203. 10.1016/j.neunet.2003.07.010. PubMed

Bracha V, Zbarska S, Parker K, Carrel A, Zenitsky G, Bloedel JR. The cerebellum and eye-blink conditioning: learning versus network performance hypotheses. Neuroscience. 2009;162:787–96. 10.1016/j.neuroscience.2008.12.042. PubMed PMC

Porras-Garcia E, Sanchez-Campusano R, Martinez-Vargas D, Dominguez-del-Toro E, Cendelin J, Vozeh F, et al. Behavioral characteristics, associative learning capabilities, and dynamic association mapping in an animal model of cerebellar degeneration. J Neurophysiol. 2010;104:346–65. 10.1152/jn.00180.2010. PubMed

Lopez-Ramos JC, Houdek Z, Cendelin J, Vozeh F, Delgado-Garcia JM. Timing correlations between cerebellar interpositus neuronal firing and classically conditioned eyelid responses in wild-type and lurcher mice. Sci Rep. 2018;8:10697. 10.1038/s41598-018-29000-w. PubMed PMC

Lalonde R. Immobility responses in lurcher mutant mice. Behav Genet. 1998;28:309–14. PubMed

Kashdan TB, Elhai JD, Breen WE. Social anxiety and disinhibition: an analysis of curiosity and social rank appraisals, approach-avoidance conflicts, and disruptive risk-taking behavior. J Anxiety Disord. 2008;22:925–39. 10.1016/j.janxdis.2007.09.009. PubMed PMC

Tuma J, Cendelin J, Vozeh F. Maternal infanticide and low maternal ability in cerebellar mutants lurcher. Neuro Endocrinol Lett. 2013;34:618–23. PubMed

Lorivel T, Gras M, Hilber P. Effects of corticosterone synthesis inhibitor Metyrapone on anxiety-related behaviors in lurcher mutant mice. Physiol Behav. 2010;101:309–14. 10.1016/j.physbeh.2010.05.011. PubMed

Lorivel T, Cendelin J, Hilber P. Familiarization effects on the behavioral disinhibition of the cerebellar lurcher mutant mice: use of the innovative dual maze. Behav Brain Res. 2021;398:112972. 10.1016/j.bbr.2020.112972. PubMed

Tadenev ALD, Burgess RW. Model validity for preclinical studies in precision medicine: precisely how precise do we need to be? Mamm Genome. 2019;30:111–22. 10.1007/s00335-019-09798-0. PubMed PMC

Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23:8432–44. 10.1523/JNEUROSCI.23-23-08432.2003. PubMed PMC

Hills LB, Masri A, Konno K, Kakegawa W, Lam AT, Lim-Melia E, et al. Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans. Neurology. 2013;81:1378–86. 10.1212/WNL.0b013e3182a841a3. PubMed PMC

Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318:1349–54. 10.1056/NEJM198805263182102. PubMed

Gil-Paterna P, Furmark T. Imaging the cerebellum in post-traumatic stress and anxiety disorders: a mini-review. Front Syst Neurosci. 2023;17:1197350. 10.3389/fnsys.2023.1197350. PubMed PMC

Ichimiya T, Okubo Y, Suhara T, Sudo Y. Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia. Biol Psychiatry. 2001;49:20–7. 10.1016/s0006-3223(00)01081-7. PubMed

Murakami JW, Courchesne E, Press GA, Yeung-Courchesne R, Hesselink JR. Reduced cerebellar hemisphere size and its relationship to vermal hypoplasia in autism. Arch Neurol. 1989;46:689–94. 10.1001/archneur.1989.00520420111032. PubMed

Okugawa G, Nobuhara K, Minami T, Takase K, Sugimoto T, Saito Y, et al. Neural disorganization in the superior cerebellar peduncle and cognitive abnormality in patients with schizophrenia: A diffusion tensor imaging study. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30:1408–12. 10.1016/j.pnpbp.2006.05.014. PubMed

McKimm E, Corkill B, Goldowitz D, Albritton LM, Homayouni R, Blaha CD, et al. Glutamate dysfunction associated with developmental cerebellar damage: relevance to autism spectrum disorders. Cerebellum. 2014;13:346–53. 10.1007/s12311-013-0541-4. PubMed PMC

Mittleman G, Goldowitz D, Heck DH, Blaha CD. Cerebellar modulation of frontal cortex dopamine efflux in mice: relevance to autism and schizophrenia. Synapse. 2008;62:544–50. 10.1002/syn.20525. PubMed PMC

Rogers TD, Dickson PE, McKimm E, Heck DH, Goldowitz D, Blaha CD, et al. Reorganization of circuits underlying cerebellar modulation of prefrontal cortical dopamine in mouse models of autism spectrum disorder. Cerebellum. 2013;12:547–56. 10.1007/s12311-013-0462-2. PubMed PMC

Ilg W, Brotz D, Burkard S, Giese MA, Schols L, Synofzik M. Long-term effects of coordinative training in degenerative cerebellar disease. Mov Disord. 2010;25:2239–46. 10.1002/mds.23222. PubMed

Miyai I, Ito M, Hattori N, Mihara M, Hatakenaka M, Yagura H, et al. Cerebellar ataxia rehabilitation trial in degenerative cerebellar diseases. Neurorehabil Neural Repair. 2012;26:515–22. 10.1177/1545968311425918. PubMed

Cendelin J, Korelusova I, Vozeh F. A preliminary study of solid embryonic cerebellar graft survival in adult B6CBA lurcher mutant and wild type mice. Anat Rec (Hoboken). 2009;292:1986–92. 10.1002/ar.20967. PubMed

Houdek Z, Cendelin J, Kulda V, Babuska V, Cedikova M, Kralickova M, et al. Intracerebellar application of P19-derived neuroprogenitor and Naive stem cells to lurcher mutant and wild type B6CBA mice. Med Sci Monit. 2012;18:Br174–80. PubMed PMC

Purkartova Z, Krakorova K, Babuska V, Tuma J, Houdek Z, Roy Choudhury N, et al. Quantification of solid embryonic cerebellar graft volume in a degenerative Ataxia model. Cerebellum. 2024;23:1811–23. 10.1007/s12311-024-01676-z. PubMed

Sucha M, Benediktova S, Tichanek F, Jedlicka J, Kapl S, Jelinkova D, et al. Experimental treatment with Edaravone in a mouse model of spinocerebellar Ataxia 1. Int J Mol Sci. 2023;24. 10.3390/ijms241310689. PubMed PMC

Cendelin J, Mitoma H. Neurotransplantation therapy. Handb Clin Neurol. 2018;155:379–91. 10.1016/B978-0-444-64189-2. 00025– 1. PubMed

Cendelin J, Babuska V, Korelusova I, Houdek Z, Vozeh F. Long-term survival of solid embryonic cerebellar grafts in lurcher mice. Neurosci Lett. 2012;515:23–7. 10.1016/j.neulet.2012.03.007. PubMed

Purkartova Z, Tichanek F, Kolinko Y, Cendelin J. Embryonic cerebellar graft morphology differs in two mouse models of cerebellar degeneration. Cerebellum. 2019;18:855–65. 10.1007/s12311-019-01067-9. PubMed

Jones J, Jaramillo-Merchan J, Bueno C, Pastor D, Viso-Leon M, Martinez S. Mesenchymal stem cells rescue purkinje cells and improve motor functions in a mouse model of cerebellar ataxia. Neurobiol Dis. 2010;40:415–23. 10.1016/j.nbd.2010.07.001. PubMed

Sauer G, Wille W, Muller WE. Binding studies in the lurcher mutant suggest an uneven distribution of putative benzodiazepine receptor subclasses in the mouse cerebellum. Neurosci Lett. 1984;48:333–8. 10.1016/0304-3940(84)90060-0. PubMed DOI

Fry JP, Rickets C, Biscoe TJ. On the location of gamma-aminobutyrate and benzodiazepine receptors in the cerebellum of the normal C3H and lurcher mutant mouse. Neuroscience. 1985;14:1091–101. 10.1016/0306-4522(85)90279-9. PubMed DOI

Lorivel T, Hilber P. Effects of chlordiazepoxide on the emotional reactivity and motor capacities in the cerebellar lurcher mutant mice. Behav Brain Res. 2006;173:122–8. 10.1016/j.bbr.2006.06.011. PubMed

Lalonde R, Joyal CC, Guastavino JM, Cote C, Botez MI. Amantadine and ketamine-induced improvement of motor coordination in lurcher mutant mice. Restor Neurol Neurosci. 1993;5:367–70. 10.3233/rnn-1993-55607. PubMed

Lorivel T, Hilber P. Motor effects of delta 9 THC in cerebellar lurcher mutant mice. Behav Brain Res. 2007;181:248–53. 10.1016/j.bbr.2007.04.011. PubMed

Stephens GJ. Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia? J Physiol. 2016;594:4631–41. 10.1113/JP271106. PubMed PMC

Gomez-Ruiz M, Rodriguez-Cueto C, Luna-Pinel E, Hernandez-Galvez M, Fernandez-Ruiz J. Endocannabinoid system in spinocerebellar Ataxia Type-3 and other Autosomal-Dominant cerebellar ataxias: potential role in pathogenesis and expected relevance as neuroprotective targets. Front Mol Neurosci. 2019;12:94. 10.3389/fnmol.2019.00094. PubMed PMC

Markvartova V, Cendelin J, Vozeh F. Effect of dimethyl sulfoxide in cerebellar mutant lurcher mice. Neurosci Lett. 2013;543:142–5. 10.1016/j.neulet.2013.03.034. PubMed

Bhatia MS, Saha R, Gautam P. Cerebellar cognitive affective syndrome: A case report. Prim Care Companion CNS Disord. 2016;18. 10.4088/PCC.15l01851. PubMed PMC

Pinel-Rios J, Perez-Saborido IM. Clinical note: cerebellar cognitive affective syndrome improvement with selective inhibitor of serotonin recaptation. Actas Esp Psiquiatr. 2022;50:122–5. PubMed PMC

Yap JL, Wachtel LE, Ahn ES, Sanz JH, Slomine BS, Pidcock FS. Treatment of cerebellar cognitive affective syndrome with Aripiprazole. J Pediatr Rehabil Med. 2012;5:233–8. 10.3233/PRM-2012-0215. PubMed

Cosme-Cruz RM, de Leon Jauregui M, Hussain M. Cerebellar cognitive affective syndrome: A case report and literature review of available treatments. Psychiatric Annals. 2022;52:35–41.

Coutelier M, Burglen L, Mundwiller E, Abada-Bendib M, Rodriguez D, Chantot-Bastaraud S, et al. GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia. Neurology. 2015;84:1751–9. 10.1212/wnl.0000000000001524. PubMed

Chort A, Alves S, Marinello M, Dufresnois B, Dornbierer JG, Tesson C, et al. Interferon beta induces clearance of mutant ataxin 7 and improves locomotion in SCA7 knock-in mice. Brain. 2013;136:1732–45. 10.1093/brain/awt061. PubMed

Correia JS, Neves-Carvalho A, Mendes-Pinheiro B, Pires J, Teixeira FG, Lima R, et al. Preclinical assessment of Mesenchymal-Stem-Cell-Based therapies in spinocerebellar Ataxia type 3. Biomedicines. 2021;9. 10.3390/biomedicines9121754. PubMed PMC

Friedrich J, Kordasiewicz HB, O’Callaghan B, Handler HP, Wagener C, Duvick L, et al. Antisense oligonucleotide-mediated ataxin-1 reduction prolongs survival in SCA1 mice and reveals disease-associated transcriptome profiles. JCI Insight. 2018;3. 10.1172/jci.insight.123193. PubMed PMC

Matsuura S, Shuvaev AN, Iizuka A, Nakamura K, Hirai H. Mesenchymal stem cells ameliorate cerebellar pathology in a mouse model of spinocerebellar ataxia type 1. Cerebellum. 2014;13:323–30. 10.1007/s12311-013-0536-1. PubMed

Nascimento-Ferreira I, Nobrega C, Vasconcelos-Ferreira A, Onofre I, Albuquerque D, Aveleira C, et al. Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado-Joseph disease. Brain. 2013;136:2173–88. 10.1093/brain/awt144. PubMed

Nobrega C, Nascimento-Ferreira I, Onofre I, Albuquerque D, Hirai H, Deglon N, et al. Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-Joseph disease Transgenic mice. PLoS ONE. 2013;8:e52396. 10.1371/journal.pone.0052396. PubMed PMC

Ghaemmaghami A, Aboyans V, Morvarid A. [Drug interactions]. J Dent Sch Natl Univ Iran. 1977;9:32–5. PubMed

Kaemmerer WF, Low WC. Cerebellar allografts survive and transiently alleviate ataxia in a Transgenic model of spinocerebellar ataxia type-1. Exp Neurol. 1999;158:301–11. 10.1006/exnr.1999.7099. PubMed

Ceylan AC, Acar Arslan E, Erdem HB, Kavus H, Arslan M, Topaloglu H. Autosomal recessive spinocerebellar ataxia 18 caused by homozygous exon 14 duplication in GRID2 and review of the literature. Acta Neurol Belg. 2021;121:1457–62. 10.1007/s13760-020-01328-z. PubMed

Grigorenko AP, Protasova MS, Lisenkova AA, Reshetov DA, Andreeva TV, Garcias GL, et al. Neurodevelopmental syndrome with intellectual disability, speech impairment, and quadrupedia is associated with glutamate receptor Delta 2 gene defect. Cells. 2022;11. 10.3390/cells11030400. PubMed PMC

Utine GE, Haliloglu G, Salanci B, Cetinkaya A, Kiper PO, Alanay Y, et al. A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy. J Child Neurol. 2013;28:926–32. 10.1177/0883073813484967. PubMed

Van Schil K, Meire F, Karlstetter M, Bauwens M, Verdin H, Coppieters F, et al. Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human Hotfoot phenotype caused by homozygous GRID2 deletion. Genet Med. 2015;17:291–9. 10.1038/gim.2014.95. PubMed

Tomey DA, Heckroth JA. Transplantation of normal embryonic cerebellar cell suspensions into the cerebellum of lurcher mutant mice. Exp Neurol. 1993;122:165–70. 10.1006/exnr.1993.1117. PubMed

Cendelin J, Cvetanovic M, Gandelman M, Hirai H, Orr HT, Pulst SM, et al. Consensus paper: strengths and weaknesses of animal models of spinocerebellar ataxias and their clinical implications. Cerebellum. 2022;21:452–81. 10.1007/s12311-021-01311-1. PubMed PMC

Manto M, Cendelin J, Strupp M, Mitoma H. Advances in cerebellar disorders: pre-clinical models, therapeutic targets, and challenges. Expert Opin Ther Targets. 2023;27:965–87. 10.1080/14728222.2023.2263911. PubMed