{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T08:12:34Z","timestamp":1769501554215,"version":"3.49.0"},"reference-count":75,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,9,18]],"date-time":"2015-09-18T00:00:00Z","timestamp":1442534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The mammalian target of rapamycin (m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>) is a key regulator of cellular growth which associates with other proteins to form two multi\u2010protein complexes called m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 and m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2. Dysregulation of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 signalling in brain is implicated in neuropathological conditions such as autism spectrum or neurodegenerative disorders. Accordingly, allosteric m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> inhibitors are currently in clinical trials for the treatment of such disorders. Here, we ablated either m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 or m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2 conditionally in Purkinje cells of the mouse cerebellum to dissect their role in the development, function and survival of these neurons. We find that the two mouse models largely differ from each other by phenotype and cellular responses. Inactivation of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2, but not of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1, led to motor coordination deficits at an early age. This phenotype correlated with developmental deficits in climbing fibre elimination and impaired dendritic self\u2010avoidance in m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2\u2010deficient Purkinje cells. In contrast, inactivation of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1, but not of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2, affected social interest of the mice and caused a progressive loss of Purkinje cells due to apoptosis. This cell loss was paralleled by age\u2010dependent motor deficits. Comparison of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1\u2010deficient Purkinje cells with those deficient for the m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 inhibitor <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>1 revealed a striking overlap in Purkinje cell degeneration and death, which included neurofilamentopathy and reactive gliosis. Altogether, our study reveals distinct roles of m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 and m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2 in Purkinje cells for mouse behaviour and the survival of neurons. Our study also highlights a convergence between the phenotypes of Purkinje cells lacking m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 activity and those expressing constitutively active m<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 due to <jats:styled-content style=\"fixed-case\">TSC<\/jats:styled-content>1 deficiency.<\/jats:p>","DOI":"10.1111\/ejn.13051","type":"journal-article","created":{"date-parts":[[2015,8,22]],"date-time":"2015-08-22T10:25:10Z","timestamp":1440239110000},"page":"2595-2612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["m<scp>TORC<\/scp>1 and m<scp>TORC<\/scp>2 have largely distinct functions in Purkinje cells"],"prefix":"10.1111","volume":"42","author":[{"given":"Nico","family":"Angliker","sequence":"first","affiliation":[{"name":"Biozentrum University of Basel Klingelbergstrasse 70 CH\u20104056 Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Burri","sequence":"additional","affiliation":[{"name":"Biozentrum University of Basel Klingelbergstrasse 70 CH\u20104056 Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Zaichuk","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean\u2010Marc","family":"Fritschy","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus A.","family":"R\u00fcegg","sequence":"additional","affiliation":[{"name":"Biozentrum University of Basel Klingelbergstrasse 70 CH\u20104056 Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,9,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.4161\/bioa.26497"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2056"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.69020737.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001113)427:2<235::AID-CNE6>3.0.CO;2-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.10.002"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012119"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.08.024"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.03.015"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90148-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-08-02974.1999"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3294-12.2013"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3546"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)61279-9"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021729"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5118-05.2006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.01.028"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.009"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1106454108"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/002215540205000401"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1405-2"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.89.183"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1529-8027.2012.00434.x"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3351"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5472.1832"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2791"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-13-04954.2000"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90147-7"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.26.15724"},{"key":"e_1_2_7_31_1","first-page":"2173","article-title":"Type\u20101 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long\u2010term depression, endocannabinoid signalling and synapse elimination","volume":"363","author":"Kano M.","year":"2008","journal-title":"P. Roy. Soc. B\u2010Biol. Sci."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.03.023"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.017"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11305"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.09.034"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.11.043"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(97)00111-1"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0955-08.2008"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4462-06.2006"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12447"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.25.14089"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.10.14.16586"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802390105"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20207"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2012.10.014"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4254"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5417.1161"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.04.043"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2011.00076"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2006.03.029"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206674200"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22148"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/14734220701490995"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02513-0"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.265"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/400_2009_8"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3757"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2851"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.12.035"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030011"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201205030"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11310"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3670"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21713"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00356-8"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.016"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07894.x"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20999"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2180"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1261-12.2012"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-7722.2002.00021.x"},{"key":"e_1_2_7_75_1","first-page":"8.24","article-title":"Simple behavioral assessment of mouse olfaction","volume":"8","author":"Yang M.","year":"2009","journal-title":"Curr. Protoc. Neurosci."},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2013.04.001"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejn.13051","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.13051","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T05:46:57Z","timestamp":1695016017000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.13051"}},"subtitle":[],"editor":[{"given":"Masahiko","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,9,18]]},"references-count":75,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,10]]}},"alternative-id":["10.1111\/ejn.13051"],"URL":"https:\/\/doi.org\/10.1111\/ejn.13051","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,18]]},"assertion":[{"value":"2015-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}