151528 20230915093956.0 pmc:PMC7117892 pmc 10.1523/JNEUROSCI.2316-19.2020 doi 0270-6474 ISSN 1529-2401 ISSN altmetric:78685898 altmetric pmid:32122952 pmid DZNE-2020-01112 English 610 Falck, Joanne P:(DE-2719)2811704 0 First author Loss of Piccolo Function in Rats Induces Cerebellar Network Dysfunction and Pontocerebellar Hypoplasia Type 3-like Phenotypes Washington, DC 2020 Soc.8825 online Crossref Society for Neuroscience 2020-03-02 print Crossref Society for Neuroscience 2020-04-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1677246422_7992 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Piccolo, a presynaptic active zone protein, is best known for its role in the regulated assembly and function of vertebrate synapses. Genetic studies suggest a further link to several psychiatric disorders as well as Pontocerebellar Hypoplasia type 3 (PCH3). We have characterized recently generated Piccolo KO (Pclogt/gt) rats. Analysis of rats of both sexes revealed a dramatic reduction in brain size compared with WT (Pclowt/wt) animals, attributed to a decrease in the size of the cerebral cortical, cerebellar, and pontine regions. Analysis of the cerebellum and brainstem revealed a reduced granule cell layer and a reduction in size of pontine nuclei. Moreover, the maturation of mossy fiber afferents from pontine neurons and the expression of the α6 GABAA receptor subunit at the mossy fiber-granule cell synapse are perturbed, as well as the innervation of Purkinje cells by cerebellar climbing fibers. Ultrastructural and functional studies revealed a reduced size of mossy fiber boutons, with fewer synaptic vesicles and altered synaptic transmission. These data imply that Piccolo is required for the normal development, maturation, and function of neuronal networks formed between the brainstem and cerebellum. Consistently, behavioral studies demonstrated that adult Pclogt/gt rats display impaired motor coordination, despite adequate performance in tasks that reflect muscle strength and locomotion. Together, these data suggest that loss of Piccolo function in patients with PCH3 could be involved in many of the observed anatomical and behavioral symptoms, and that the further analysis of these animals could provide fundamental mechanistic insights into this devastating disorder. 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 0 2020-10-01 Crossref https://creativecommons.org/licenses/by-nc-sa/4.0/ Dataset connected to CrossRef Animals MeSH Cerebellum: metabolism MeSH Cerebellum: pathology MeSH Cerebellum: physiopathology MeSH Cytoskeletal Proteins: metabolism MeSH Disease Models, Animal MeSH Female MeSH Gene Knockout Techniques MeSH Male MeSH Neuropeptides: metabolism MeSH Olivopontocerebellar Atrophies MeSH Phenotype MeSH Rats MeSH Bruns, Christine P:(DE-2719)2811027 1 Hoffmann, Sheila Sook-Hi P:(DE-2719)2811236 2 Straub, Isabelle 3 Plautz, Erik J. 4 Orlando, Marta 5 Munawar, Humaira 6 Rivalan, Marion 7 Winter, York 8 Izsvák, Zsuzsanna 9 Schmitz, Dietmar P:(DE-HGF)0 10 Hamra, F. Kent 11 Hallermann, Stefan 12 Garner, Craig Curtis P:(DE-2719)2810922 13 Corresponding author Ackermann, Frauke P:(DE-2719)2810967 14 Last author 10.1523/jneurosci.2316-19.2020 Society for Neuroscience 2020-03-02 14 2943-2959 journal-article Crossref The Journal of Neuroscience 40 2020 0270-6474 10.1523/JNEUROSCI.2316-19.2020 Vol. 40, no. 14, p. 2943 - 2959 PERI:(DE-600)1475274-8 14 2943-2959 The journal of neuroscience 40 2020 0270-6474 https://www.jneurosci.org/content/40/14/2943.abstract VDB oai:pub.dzne.de:151528 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 0 P:(DE-2719)2811704 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2811027 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2811236 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 13 P:(DE-2719)2810922 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 14 P:(DE-2719)2810967 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 0 2020 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2020-02-27 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2020-02-27 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-13 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-13 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-13 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-13 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-13 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2022-11-13 JCR StatID:(DE-HGF)0100 StatID J NEUROSCI : 2021 2022-11-13 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-13 Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-13 IF >= 5 StatID:(DE-HGF)9905 StatID J NEUROSCI : 2021 2022-11-13 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interaction 1 journal VDB I:(DE-2719)1810001 I:(DE-2719)1813004 UNRESTRICTED 10.7554/eLife.46629 -- missing cx lookup -- Crossref 10.1083/jcb.200511054 -- missing cx lookup -- Crossref 10.1212/WNL.0000000000001523 -- missing cx lookup -- Crossref 10.1038/nrn1646 -- missing cx lookup -- Crossref 10.1113/jphysiol.1996.sp021806 -- missing cx lookup -- Crossref 10.1016/j.neures.2017.10.013 -- missing cx lookup -- Crossref Cases-Langhoff 1996 Crossref Cases-Langhoff 1996 10.1038/srep20201 -- missing cx lookup -- Crossref 10.1201/NOE1420052343.ch8 -- missing cx lookup -- Crossref Curzon P , Zhang M , Radek RJ , Fox GB (2009) The behavioral assessment of sensorimotor processes in the mouse: acoustic startle, sensory gating, locomotor activity, rotarod, and beam walking. In: Methods of behavior analysis in neuroscience ( Buccafusco JJ , ed). Boca Raton, FL: CRC. 10.1007/s00415-009-0094-0 -- missing cx lookup -- Crossref 10.1007/bf00235211 -- missing cx lookup -- Crossref 10.3389/fncel.2019.00289 -- missing cx lookup -- Crossref 10.1016/S0736-5748(02)00046-1 -- missing cx lookup -- Crossref 10.1016/S0896-6273(00)80883-1 -- missing cx lookup -- Crossref 10.1016/j.cellsig.2009.11.021 -- missing cx lookup -- Crossref 10.3389/fnsyn.2015.00019 -- missing cx lookup -- Crossref 10.1016/S0092-8674(00)80689-3 -- missing cx lookup -- Crossref 10.1111/j.1469-7793.1998.391bw.x -- missing cx lookup -- Crossref 10.1016/j.neuron.2009.06.008 -- missing cx lookup -- Crossref 10.1007/s00441-011-1233-3 -- missing cx lookup -- Crossref 10.1124/mol.51.4.588 -- missing cx lookup -- Crossref 10.1371/journal.pone.0039710 -- missing cx lookup -- Crossref 10.1073/pnas.1511513113 -- missing cx lookup -- Crossref 10.15252/embj.201488796 -- missing cx lookup -- Crossref 10.1038/nmeth.1332 -- missing cx lookup -- Crossref 10.1038/nmeth.1461 -- missing cx lookup -- Crossref 10.1007/BF00305102 -- missing cx lookup -- Crossref 10.1007/s12311-015-0724-2 -- missing cx lookup -- Crossref 10.1152/jn.1998.80.5.2521 -- missing cx lookup -- Crossref 10.1177/0883073810380047 -- missing cx lookup -- Crossref 10.1007/s12035-019-01785-5 -- missing cx lookup -- Crossref Mayhew 1996 Crossref Mayhew 1996 10.1101/405985 -- missing cx lookup -- Crossref Medrano GA , Singh M , Plautz EJ , Good LB , Chapman KM , Chaudhary J , Jaichander P , Powell HM , Pudasaini A , Shelton JM , Richardson JA , Xie XJ , Ivics Z , Braun C , Ackermann F , Garner CC , Izsvák Z , Hamra FK (2019) Mutant screen reveals depression-associated Piccolo's control over brain-gonad cross talk and reproductive behavior. bioRxiv: 405985. 10.3791/1204 -- missing cx lookup -- Crossref 10.1016/j.mod.2017.06.002 -- missing cx lookup -- Crossref 10.1046/j.1460-9568.2003.02698.x -- missing cx lookup -- Crossref 10.1073/pnas.1002307107 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.2038-18.2019 -- missing cx lookup -- Crossref 10.1093/brain/awq287 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.16-01-00103.1996 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.18-05-01693.1998 -- missing cx lookup -- Crossref 10.1212/01.WNL.0000068548.58498.41 -- missing cx lookup -- Crossref 10.3389/fncel.2014.00259 -- missing cx lookup -- Crossref 10.3389/fninf.2018.00014 -- missing cx lookup -- Crossref 10.1002/ajmg.c.31403 -- missing cx lookup -- Crossref 10.1146/annurev.neuro.31.060407.125649 -- missing cx lookup -- Crossref 10.1146/annurev.neuro.26.043002.094940 -- missing cx lookup -- Crossref 10.1038/nmeth.2019 -- missing cx lookup -- Crossref 10.1152/jn.1992.67.3.547 -- missing cx lookup -- Crossref 10.1016/B978-0-12-369497-3.10011-1 -- missing cx lookup -- Crossref Sillitoe R , Fu Y , Watson, C (2012) Cerebellum. San Diego: Academic. 10.1016/S0896-6273(01)00395-6 -- missing cx lookup -- Crossref 10.1101/cshperspect.a005736 -- missing cx lookup -- Crossref 10.1126/science.1260419 -- missing cx lookup -- Crossref 10.1016/S0166-2236(98)01318-6 -- missing cx lookup -- Crossref 10.1371/journal.pone.0120093 -- missing cx lookup -- Crossref 10.1146/annurev.neuro.27.070203.144336 -- missing cx lookup -- Crossref 10.1038/emboj.2013.27 -- missing cx lookup -- Crossref 10.1016/S0960-9822(99)80195-X -- missing cx lookup -- Crossref 10.1016/S0092-8674(00)81779-1 -- missing cx lookup -- Crossref 10.1523/JNEUROSCI.23-06-02182.2003 -- missing cx lookup -- Crossref 10.1007/s002340050334 -- missing cx lookup -- Crossref 10.1016/S0896-6273(01)00185-4 -- missing cx lookup -- Crossref