{"status":"public","project":[{"_id":"267DFB90-B435-11E9-9278-68D0E5697425","name":"Plasticity in the cerebellum: Which molecular mechanisms are behind physiological learning?"}],"department":[{"_id":"GradSch"},{"_id":"RySh"}],"oa_version":"Published Version","doi":"10.15479/at:ista:12809","month":"04","alternative_title":["ISTA Thesis"],"year":"2023","abstract":[{"text":"Understanding the mechanisms of learning and memory formation has always been one of\r\nthe main goals in neuroscience. Already Pavlov (1927) in his early days has used his classic\r\nconditioning experiments to study the neural mechanisms governing behavioral adaptation.\r\nWhat was not known back then was that the part of the brain that is largely responsible for\r\nthis type of associative learning is the cerebellum.\r\nSince then, plenty of theories on cerebellar learning have emerged. Despite their differences,\r\none thing they all have in common is that learning relies on synaptic and intrinsic plasticity.\r\nThe goal of my PhD project was to unravel the molecular mechanisms underlying synaptic\r\nplasticity in two synapses that have been shown to be implicated in motor learning, in an\r\neffort to understand how learning and memory formation are processed in the cerebellum.\r\nOne of the earliest and most well-known cerebellar theories postulates that motor learning\r\nlargely depends on long-term depression at the parallel fiber-Purkinje cell (PC-PC) synapse.\r\nHowever, the discovery of other types of plasticity in the cerebellar circuitry, like long-term\r\npotentiation (LTP) at the PC-PC synapse, potentiation of molecular layer interneurons (MLIs),\r\nand plasticity transfer from the cortex to the cerebellar/ vestibular nuclei has increased the\r\npopularity of the idea that multiple sites of plasticity might be involved in learning.\r\nStill a lot remains unknown about the molecular mechanisms responsible for these types of\r\nplasticity and whether they occur during physiological learning.\r\nIn the first part of this thesis we have analyzed the variation and nanodistribution of voltagegated calcium channels (VGCCs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid\r\ntype glutamate receptors (AMPARs) on the parallel fiber-Purkinje cell synapse after vestibuloocular reflex phase reversal adaptation, a behavior that has been suggested to rely on PF-PC\r\nLTP. We have found that on the last day of adaptation there is no learning trace in form of\r\nVGCCs nor AMPARs variation at the PF-PC synapse, but instead a decrease in the number of\r\nPF-PC synapses. These data seem to support the view that learning is only stored in the\r\ncerebellar cortex in an initial learning phase, being transferred later to the vestibular nuclei.\r\nNext, we have studied the role of MLIs in motor learning using a relatively simple and well characterized behavioral paradigm – horizontal optokinetic reflex (HOKR) adaptation. We\r\nhave found behavior-induced MLI potentiation in form of release probability increase that\r\ncould be explained by the increase of VGCCs at the presynaptic side. Our results strengthen\r\nthe idea of distributed cerebellar plasticity contributing to learning and provide a novel\r\nmechanism for release probability increase. ","lang":"eng"}],"title":"Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning","_id":"12809","file":[{"date_updated":"2024-04-08T22:30:03Z","date_created":"2023-04-07T06:16:06Z","creator":"cchlebak","file_id":"12814","file_name":"Thesis_CatarinaAlcarva_final pdfA.pdf","file_size":9881969,"relation":"main_file","embargo":"2024-04-07","content_type":"application/pdf","checksum":"35b5997d2b0acb461f9d33d073da0df5","access_level":"open_access"},{"access_level":"closed","content_type":"application/pdf","checksum":"81198f63c294890f6d58e8b29782efdc","embargo_to":"open_access","relation":"source_file","file_size":44201583,"file_name":"Thesis_CatarinaAlcarva_final_for printing.pdf","date_updated":"2024-04-08T22:30:03Z","date_created":"2023-04-07T06:17:11Z","file_id":"12815","creator":"cchlebak"},{"file_name":"Thesis_CatarinaAlcarva_final.docx","relation":"source_file","file_size":84731244,"embargo_to":"open_access","creator":"cchlebak","file_id":"12816","date_created":"2023-04-07T06:18:05Z","date_updated":"2024-04-08T22:30:03Z","access_level":"closed","checksum":"0317bf7f457bb585f99d453ffa69eb53","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document"}],"ddc":["570"],"file_date_updated":"2024-04-08T22:30:03Z","language":[{"iso":"eng"}],"publisher":"Institute of Science and Technology Austria","page":"115","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"apa":"Alcarva, C. (2023). <i>Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/at:ista:12809\">https://doi.org/10.15479/at:ista:12809</a>","ieee":"C. Alcarva, “Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning,” Institute of Science and Technology Austria, 2023.","ista":"Alcarva C. 2023. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. Institute of Science and Technology Austria.","mla":"Alcarva, Catarina. <i>Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/at:ista:12809\">10.15479/at:ista:12809</a>.","short":"C. Alcarva, Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning, Institute of Science and Technology Austria, 2023.","chicago":"Alcarva, Catarina. “Plasticity in the Cerebellum: What Molecular Mechanisms Are behind Physiological Learning.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/at:ista:12809\">https://doi.org/10.15479/at:ista:12809</a>.","ama":"Alcarva C. Plasticity in the cerebellum: What molecular mechanisms are behind physiological learning. 2023. doi:<a href=\"https://doi.org/10.15479/at:ista:12809\">10.15479/at:ista:12809</a>"},"publication_status":"published","oa":1,"type":"dissertation","supervisor":[{"last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi"}],"date_updated":"2024-04-08T22:30:04Z","publication_identifier":{"issn":["2663 - 337X"]},"author":[{"last_name":"Alcarva","first_name":"Catarina","id":"3A96634C-F248-11E8-B48F-1D18A9856A87","full_name":"Alcarva, Catarina"}],"date_created":"2023-04-06T07:54:09Z","date_published":"2023-04-06T00:00:00Z","article_processing_charge":"No","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"PreCl"}],"has_accepted_license":"1","day":"06","degree_awarded":"PhD"}