[{"has_accepted_license":"1","article_processing_charge":"No","day":"21","keyword":["Cognitive Neuroscience","Neurology (clinical)","Neurology"],"scopus_import":"1","date_published":"2022-09-21T00:00:00Z","article_type":"original","citation":{"chicago":"Martín-Belmonte, Alejandro, Carolina Aguado, Rocío Alfaro-Ruiz, Ana Esther Moreno-Martínez, Luis de la Ossa, Ester Aso, Laura Gómez-Acero, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy. Springer Nature, 2022. https://doi.org/10.1186/s13195-022-01078-5.","mla":"Martín-Belmonte, Alejandro, et al. “Nanoscale Alterations in GABAB Receptors and GIRK Channel Organization on the Hippocampus of APP/PS1 Mice.” Alzheimer’s Research & Therapy, vol. 14, 136, Springer Nature, 2022, doi:10.1186/s13195-022-01078-5.","short":"A. Martín-Belmonte, C. Aguado, R. Alfaro-Ruiz, A.E. Moreno-Martínez, L. de la Ossa, E. Aso, L. Gómez-Acero, R. Shigemoto, Y. Fukazawa, F. Ciruela, R. Luján, Alzheimer’s Research & Therapy 14 (2022).","ista":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, Moreno-Martínez AE, de la Ossa L, Aso E, Gómez-Acero L, Shigemoto R, Fukazawa Y, Ciruela F, Luján R. 2022. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 14, 136.","apa":"Martín-Belmonte, A., Aguado, C., Alfaro-Ruiz, R., Moreno-Martínez, A. E., de la Ossa, L., Aso, E., … Luján, R. (2022). Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. Springer Nature. https://doi.org/10.1186/s13195-022-01078-5","ieee":"A. Martín-Belmonte et al., “Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice,” Alzheimer’s Research & Therapy, vol. 14. Springer Nature, 2022.","ama":"Martín-Belmonte A, Aguado C, Alfaro-Ruiz R, et al. Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice. Alzheimer’s Research & Therapy. 2022;14. doi:10.1186/s13195-022-01078-5"},"publication":"Alzheimer's Research & Therapy","abstract":[{"lang":"eng","text":"Alzheimer’s disease (AD) is characterized by a reorganization of brain activity determining network hyperexcitability and loss of synaptic plasticity. Precisely, a dysfunction in metabotropic GABAB receptor signalling through G protein-gated inwardly rectifying K+ (GIRK or Kir3) channels on the hippocampus has been postulated. Thus, we determined the impact of amyloid-β (Aβ) pathology in GIRK channel density, subcellular distribution, and its association with GABAB receptors in hippocampal CA1 pyramidal neurons from the APP/PS1 mouse model using quantitative SDS-digested freeze-fracture replica labelling (SDS-FRL) and proximity ligation in situ assay (P-LISA). In wild type mice, single SDS-FRL detection revealed a similar dendritic gradient for GIRK1 and GIRK2 in CA1 pyramidal cells, with higher densities in spines, and GIRK3 showed a lower and uniform distribution. Double SDS-FRL showed a co-clustering of GIRK2 and GIRK1 in post- and presynaptic compartments, but not for GIRK2 and GIRK3. Likewise, double GABAB1 and GIRK2 SDS-FRL detection displayed a high degree of co-clustering in nanodomains (40–50 nm) mostly in spines and axon terminals. In APP/PS1 mice, the density of GIRK2 and GIRK1, but not for GIRK3, was significantly reduced along the neuronal surface of CA1 pyramidal cells and in axon terminals contacting them. Importantly, GABAB1 and GIRK2 co-clustering was not present in APP/PS1 mice. Similarly, P-LISA experiments revealed a significant reduction in GABAB1 and GIRK2 interaction on the hippocampus of this animal model. Overall, our results provide compelling evidence showing a significant reduction on the cell surface density of pre- and postsynaptic GIRK1 and GIRK2, but not GIRK3, and a decline in GABAB receptors and GIRK2 channels co-clustering in hippocampal pyramidal neurons from APP/PS1 mice, thus suggesting that a disruption in the GABAB receptor–GIRK channel membrane assembly causes dysregulation in the GABAB signalling via GIRK channels in this AD animal model."}],"type":"journal_article","oa_version":"Published Version","file":[{"checksum":"88e49715ad6a1abf0fdb27efd65368dc","success":1,"date_updated":"2023-01-27T07:53:18Z","date_created":"2023-01-27T07:53:18Z","relation":"main_file","file_id":"12413","file_size":11013325,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2022_AlzheimersResearch_MartinBelmont.pdf"}],"intvolume":" 14","ddc":["570"],"status":"public","title":"Nanoscale alterations in GABAB receptors and GIRK channel organization on the hippocampus of APP/PS1 mice","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12212","publication_identifier":{"issn":["1758-9193"]},"month":"09","language":[{"iso":"eng"}],"doi":"10.1186/s13195-022-01078-5","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000857985500001"]},"file_date_updated":"2023-01-27T07:53:18Z","article_number":"136","volume":14,"date_updated":"2023-08-04T09:23:10Z","date_created":"2023-01-16T09:45:51Z","author":[{"first_name":"Alejandro","last_name":"Martín-Belmonte","full_name":"Martín-Belmonte, Alejandro"},{"full_name":"Aguado, Carolina","first_name":"Carolina","last_name":"Aguado"},{"full_name":"Alfaro-Ruiz, Rocío","first_name":"Rocío","last_name":"Alfaro-Ruiz"},{"full_name":"Moreno-Martínez, Ana Esther","last_name":"Moreno-Martínez","first_name":"Ana Esther"},{"first_name":"Luis","last_name":"de la Ossa","full_name":"de la Ossa, Luis"},{"full_name":"Aso, Ester","last_name":"Aso","first_name":"Ester"},{"full_name":"Gómez-Acero, Laura","first_name":"Laura","last_name":"Gómez-Acero"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"},{"last_name":"Fukazawa","first_name":"Yugo","full_name":"Fukazawa, Yugo"},{"last_name":"Ciruela","first_name":"Francisco","full_name":"Ciruela, Francisco"},{"full_name":"Luján, Rafael","last_name":"Luján","first_name":"Rafael"}],"department":[{"_id":"RySh"}],"publisher":"Springer Nature","publication_status":"published","acknowledgement":"We thank Ms. Diane Latawiec for the English revision of the manuscript. Funding sources were the Spanish Ministerio de Economía y Competitividad, Junta de Comunidades de Castilla-La Mancha (Spain), and Life Science Innovation Center at University of Fukui. We thank Centres de Recerca de Catalunya (CERCA) Programme/Generalitat de Catalunya for IDIBELL institutional support. We thank Hitoshi Takagi and Takako Maegawa at the University of Fukui for their technical assistance on SDS-FRL experiments.\r\nThis work was supported by grants from the Spanish Ministerio de Economía y Competitividad (BFU2015-63769-R, RTI2018-095812-B-I00, and PID2021-125875OB-I00) and Junta de Comunidades de Castilla-La Mancha (SBPLY/17/180501/000229 and SBPLY/21/180501/000064) to RL, Life Science Innovation Center at University of Fukui and JSPS KAKENHI (Grant Numbers 16H04662, 19H03323, and 20H05058) to YF, and Margarita Salas fellowship from Ministerio de Universidades and Universidad de Castilla-La Mancha to AMB.","year":"2022"},{"year":"2022","pmid":1,"publication_status":"published","department":[{"_id":"RySh"}],"publisher":"Wiley","author":[{"last_name":"Thayyil","first_name":"Sampreeth","full_name":"Thayyil, Sampreeth"},{"full_name":"Nishigami, Yukinori","last_name":"Nishigami","first_name":"Yukinori"},{"id":"C94881D2-008F-11EA-8E08-2637E6697425","last_name":"Islam","first_name":"Muhammad J","full_name":"Islam, Muhammad J"},{"full_name":"Hashim, P. K.","first_name":"P. K.","last_name":"Hashim"},{"full_name":"Furuta, Ken'Ya","first_name":"Ken'Ya","last_name":"Furuta"},{"full_name":"Oiwa, Kazuhiro","last_name":"Oiwa","first_name":"Kazuhiro"},{"full_name":"Yu, Jian","first_name":"Jian","last_name":"Yu"},{"full_name":"Yao, Min","first_name":"Min","last_name":"Yao"},{"full_name":"Nakagaki, Toshiyuki","first_name":"Toshiyuki","last_name":"Nakagaki"},{"full_name":"Tamaoki, Nobuyuki","last_name":"Tamaoki","first_name":"Nobuyuki"}],"date_updated":"2023-10-03T10:58:31Z","date_created":"2022-04-24T22:01:44Z","volume":28,"article_number":"e202200807","external_id":{"isi":["000781658800001"],"pmid":["35332959"]},"oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1002/chem.202200807"}],"quality_controlled":"1","isi":1,"doi":"10.1002/chem.202200807","language":[{"iso":"eng"}],"month":"05","publication_identifier":{"eissn":["15213765"],"issn":["09476539"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11333","title":"Dynamic control of microbial movement by photoswitchable ATP antagonists","status":"public","intvolume":" 28","oa_version":"Published Version","type":"journal_article","abstract":[{"text":"Adenosine triphosphate (ATP) is the energy source for various biochemical processes and biomolecular motors in living things. Development of ATP antagonists and their stimuli-controlled actions offer a novel approach to regulate biological processes. Herein, we developed azobenzene-based photoswitchable ATP antagonists for controlling the activity of motor proteins; cytoplasmic and axonemal dyneins. The new ATP antagonists showed reversible photoswitching of cytoplasmic dynein activity in an in vitro dynein-microtubule system due to the trans and cis photoisomerization of their azobenzene segment. Importantly, our ATP antagonists reversibly regulated the axonemal dynein motor activity for the force generation in a demembranated model of Chlamydomonas reinhardtii. We found that the trans and cis isomers of ATP antagonists significantly differ in their affinity to the ATP binding site.","lang":"eng"}],"issue":"30","publication":"Chemistry - A European Journal","citation":{"short":"S. Thayyil, Y. Nishigami, M.J. Islam, P.K. Hashim, K. Furuta, K. Oiwa, J. Yu, M. Yao, T. Nakagaki, N. Tamaoki, Chemistry - A European Journal 28 (2022).","mla":"Thayyil, Sampreeth, et al. “Dynamic Control of Microbial Movement by Photoswitchable ATP Antagonists.” Chemistry - A European Journal, vol. 28, no. 30, e202200807, Wiley, 2022, doi:10.1002/chem.202200807.","chicago":"Thayyil, Sampreeth, Yukinori Nishigami, Muhammad J Islam, P. K. Hashim, Ken’Ya Furuta, Kazuhiro Oiwa, Jian Yu, Min Yao, Toshiyuki Nakagaki, and Nobuyuki Tamaoki. “Dynamic Control of Microbial Movement by Photoswitchable ATP Antagonists.” Chemistry - A European Journal. Wiley, 2022. https://doi.org/10.1002/chem.202200807.","ama":"Thayyil S, Nishigami Y, Islam MJ, et al. Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. 2022;28(30). doi:10.1002/chem.202200807","ieee":"S. Thayyil et al., “Dynamic control of microbial movement by photoswitchable ATP antagonists,” Chemistry - A European Journal, vol. 28, no. 30. Wiley, 2022.","apa":"Thayyil, S., Nishigami, Y., Islam, M. J., Hashim, P. K., Furuta, K., Oiwa, K., … Tamaoki, N. (2022). Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. Wiley. https://doi.org/10.1002/chem.202200807","ista":"Thayyil S, Nishigami Y, Islam MJ, Hashim PK, Furuta K, Oiwa K, Yu J, Yao M, Nakagaki T, Tamaoki N. 2022. Dynamic control of microbial movement by photoswitchable ATP antagonists. Chemistry - A European Journal. 28(30), e202200807."},"article_type":"original","date_published":"2022-05-25T00:00:00Z","scopus_import":"1","day":"25","article_processing_charge":"No"},{"day":"16","has_accepted_license":"1","article_processing_charge":"No","date_published":"2022-05-16T00:00:00Z","page":"108","citation":{"ama":"Jevtic M. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. 2022. doi:10.15479/at:ista:11393","apa":"Jevtic, M. (2022). Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:11393","ieee":"M. Jevtic, “Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus,” Institute of Science and Technology Austria, 2022.","ista":"Jevtic M. 2022. Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus. Institute of Science and Technology Austria.","short":"M. Jevtic, Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus, Institute of Science and Technology Austria, 2022.","mla":"Jevtic, Marijo. Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:11393.","chicago":"Jevtic, Marijo. “Contextual Fear Learning Induced Changes in AMPA Receptor Subtypes along the Proximodistal Axis in Dorsal Hippocampus.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:11393."},"abstract":[{"lang":"eng","text":"AMPA receptors (AMPARs) mediate fast excitatory neurotransmission and their role is\r\nimplicated in complex processes such as learning and memory and various neurological\r\ndiseases. These receptors are composed of different subunits and the subunit composition can\r\naffect channel properties, receptor trafficking and interaction with other associated proteins.\r\nUsing the high sensitivity SDS-digested freeze-fracture replica labeling (SDS-FRL) for\r\nelectron microscopy I investigated the number, density, and localization of AMPAR subunits,\r\nGluA1, GluA2, GluA3, and GluA1-3 (panAMPA) in pyramidal cells in the CA1 area of mouse\r\nhippocampus. I have found that the immunogold labeling for all of these subunits in the\r\npostsynaptic sites was highest in stratum radiatum and lowest in stratum lacunosummoleculare. The labeling density for the all subunits in the extrasynaptic sites showed a gradual\r\nincrease from the pyramidal cell soma towards the distal part of stratum radiatum. The densities\r\nof extrasynaptic GluA1, GluA2 and panAMPA labeling reached 10-15% of synaptic densities,\r\nwhile the ratio of extrasynaptic labeling for GluA3 was significantly lower compared than those\r\nfor other subunits. The labeling patterns for GluA1, GluA2 and GluA1-3 are similar and their\r\ndensities were higher in the periphery than center of synapses. In contrast, the GluA3-\r\ncontaining receptors were more centrally localized compared to the GluA1- and GluA2-\r\ncontaining receptors.\r\nThe hippocampus plays a central role in learning and memory. Contextual learning has been\r\nshown to require the delivery of AMPA receptors to CA1 synapses in the dorsal hippocampus.\r\nHowever, proximodistal heterogeneity of this plasticity and particular contribution of different\r\nAMPA receptor subunits are not fully understood. By combining inhibitory avoidance task, a\r\nhippocampus-dependent contextual fear-learning paradigm, with SDS-FRL, I have revealed an\r\nincrease in synaptic density specific to GluA1-containing AMPA receptors in the CA1 area.\r\nThe intrasynaptic distribution of GluA1 also changed from the periphery to center-preferred\r\npattern. Furthermore, this synaptic plasticity was evident selectively in stratum radiatum but\r\nnot stratum oriens, and in the CA1 subregion proximal but not distal to CA2. These findings\r\nfurther contribute to our understanding of how specific hippocampal subregions and AMPA\r\nreceptor subunits are involved in physiological learning.\r\nAlthough the immunolabeling results above shed light on subunit-specific plasticity in\r\nAMPAR distribution, no tools to visualize and study the subunit composition at the single\r\nchannel level in situ have been available. Electron microscopy with conventional immunogold\r\nlabeling approaches has limitations in the single channel analysis because of the large size of\r\nantibodies and steric hindrance hampering multiple subunit labeling of single channels. I\r\nmanaged to develop a new chemical labeling system using a short peptide tag and small\r\nsynthetic probes, which form specific covalent bond with a cysteine residue in the tag fused to\r\nproteins of interest (reactive tag system). I additionally made substantial progress into adapting\r\nthis system for AMPA receptor subunits."}],"alternative_title":["ISTA Thesis"],"type":"dissertation","oa_version":"Published Version","file":[{"checksum":"8fc695d88020d70d231dad0e9f10b138","date_updated":"2023-05-17T22:30:03Z","date_created":"2022-05-17T09:08:06Z","relation":"source_file","file_id":"11395","file_size":56427603,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"cchlebak","access_level":"closed","embargo_to":"open_access","file_name":"MJ thesis.docx"},{"checksum":"c1dd20a1aece521b3500607b00e463d6","date_updated":"2023-05-17T22:30:03Z","date_created":"2022-05-17T12:09:25Z","relation":"main_file","embargo":"2023-05-16","file_id":"11397","content_type":"application/pdf","file_size":4351981,"creator":"cchlebak","access_level":"open_access","file_name":"MJ_thesis_PDFA.pdf"}],"title":"Contextual fear learning induced changes in AMPA receptor subtypes along the proximodistal axis in dorsal hippocampus","ddc":["570"],"status":"public","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"11393","month":"05","publication_identifier":{"issn":["2663-337X"]},"supervisor":[{"full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","last_name":"Shigemoto","first_name":"Ryuichi"}],"degree_awarded":"PhD","acknowledged_ssus":[{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"doi":"10.15479/at:ista:11393","oa":1,"file_date_updated":"2023-05-17T22:30:03Z","date_updated":"2023-09-07T14:53:44Z","date_created":"2022-05-17T08:57:41Z","author":[{"full_name":"Jevtic, Marijo","id":"4BE3BC94-F248-11E8-B48F-1D18A9856A87","last_name":"Jevtic","first_name":"Marijo"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7391"}]},"publication_status":"published","department":[{"_id":"GradSch"},{"_id":"RySh"}],"publisher":"Institute of Science and Technology Austria","year":"2022"},{"month":"01","doi":"10.1016/j.cub.2020.09.074","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000614361000020"]},"quality_controlled":"1","isi":1,"project":[{"grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"}],"file_date_updated":"2020-10-19T13:31:28Z","ec_funded":1,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","author":[{"full_name":"Fredes Tolorza, Felipe A","id":"384825DA-F248-11E8-B48F-1D18A9856A87","last_name":"Fredes Tolorza","first_name":"Felipe A"},{"id":"371B3D6E-F248-11E8-B48F-1D18A9856A87","last_name":"Silva Sifuentes","first_name":"Maria A","full_name":"Silva Sifuentes, Maria A"},{"full_name":"Koppensteiner, Peter","first_name":"Peter","last_name":"Koppensteiner","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Kenta","last_name":"Kobayashi","full_name":"Kobayashi, Kenta"},{"orcid":"0000-0002-3937-1330","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","last_name":"Jösch","first_name":"Maximilian A","full_name":"Jösch, Maximilian A"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto"}],"related_material":{"link":[{"url":"https://ist.ac.at/en/news/remembering-novelty/","description":"News on IST Homepage","relation":"press_release"}]},"date_created":"2020-02-28T10:56:18Z","date_updated":"2023-08-04T10:47:11Z","volume":31,"year":"2021","acknowledgement":"We thank Peter Jonas and Peter Somogyi for critically reading the manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L. Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst, and Laura Burnett for technical assistance, as well as Robert Beattie for imaging assistance. This work was supported by a European Research Council Advanced Grant 694539 to R.S.","publication_status":"published","department":[{"_id":"MaJö"},{"_id":"RySh"}],"publisher":"Elsevier","day":"11","has_accepted_license":"1","article_processing_charge":"No","date_published":"2021-01-11T00:00:00Z","publication":"Current Biology","citation":{"ieee":"F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation,” Current Biology, vol. 31, no. 1. Elsevier, p. P25–38.E5, 2021.","apa":"Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi, K., Jösch, M. A., & Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. Elsevier. https://doi.org/10.1016/j.cub.2020.09.074","ista":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 31(1), P25–38.E5.","ama":"Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation. Current Biology. 2021;31(1):P25-38.E5. doi:10.1016/j.cub.2020.09.074","chicago":"Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner, Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology. Elsevier, 2021. https://doi.org/10.1016/j.cub.2020.09.074.","short":"F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi, M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5.","mla":"Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates Novelty-Induced Contextual Memory Formation.” Current Biology, vol. 31, no. 1, Elsevier, 2021, p. P25–38.E5, doi:10.1016/j.cub.2020.09.074."},"article_type":"original","page":"P25-38.E5","abstract":[{"lang":"eng","text":"Novelty facilitates formation of memories. The detection of novelty and storage of contextual memories are both mediated by the hippocampus, yet the mechanisms that link these two functions remain to be defined. Dentate granule cells (GCs) of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual memory. However, their key excitatory inputs from the entorhinal cortex are not responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally regulates novelty-induced contextual memory acquisition. Our results show that ventral MCs activity controls memory formation through an intra-hippocampal interaction mechanism gated by novelty."}],"issue":"1","type":"journal_article","oa_version":"Published Version","file":[{"checksum":"b7b9c8bc84a08befce365c675229a7d1","success":1,"date_created":"2020-10-19T13:31:28Z","date_updated":"2020-10-19T13:31:28Z","relation":"main_file","file_id":"8678","file_size":4915964,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2021_CurrentBiology_Fredes.pdf"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7551","status":"public","ddc":["570"],"title":"Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation","intvolume":" 31"},{"acknowledgement":"We thank Arnold Schwartz for providing α2δ-1 knockout mice; Ariane Benedetti, Sabine Baumgartner, Sandra Demetz, and Irene Mahlknecht for technical support; Nadine Ortner and Andreas Lieb for electrophysiological experiments; the team of the Electron Microscopy Facility at the Institute of Science and Technology Austria for technical support related to ultrastructural analysis; Hermann Dietrich and Anja Beierfuß and her team for animal care; Jutta Engel and Jörg Striessnig for critical discussions; and Bruno Benedetti and Bernhard Flucher for critical discussions and reading the manuscript. This study was supported by Austrian Science Fund Grants P24079, F44060, F44150, and DOC30-B30 (to G.J.O.) and T855 (to M.C.), European Research Council Grant AdG 694539 (to R.S.), Deutsche Forschungsgemeinschaft\r\nGrant SFB1348-TP A03 (to M.M.), and Interdisziplinäre Zentrum für Klinische Forschung Münster Grant Mi3/004/19 (to M.M.). This work is part of the PhD theses of C.L.S., S.M.G., and C.A.","year":"2021","publication_status":"published","department":[{"_id":"EM-Fac"},{"_id":"RySh"}],"publisher":"National Academy of Sciences","author":[{"last_name":"Schöpf","first_name":"Clemens L.","full_name":"Schöpf, Clemens L."},{"last_name":"Ablinger","first_name":"Cornelia","full_name":"Ablinger, Cornelia"},{"first_name":"Stefanie M.","last_name":"Geisler","full_name":"Geisler, Stefanie M."},{"first_name":"Ruslan I.","last_name":"Stanika","full_name":"Stanika, Ruslan I."},{"first_name":"Marta","last_name":"Campiglio","full_name":"Campiglio, Marta"},{"id":"3F99E422-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9735-5315","first_name":"Walter","last_name":"Kaufmann","full_name":"Kaufmann, Walter"},{"last_name":"Nimmervoll","first_name":"Benedikt","full_name":"Nimmervoll, Benedikt"},{"last_name":"Schlick","first_name":"Bettina","full_name":"Schlick, Bettina"},{"full_name":"Brockhaus, Johannes","last_name":"Brockhaus","first_name":"Johannes"},{"full_name":"Missler, Markus","last_name":"Missler","first_name":"Markus"},{"full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Obermair, Gerald J.","last_name":"Obermair","first_name":"Gerald J."}],"date_created":"2021-04-18T22:01:40Z","date_updated":"2023-08-08T13:08:47Z","volume":118,"file_date_updated":"2021-04-19T10:10:56Z","ec_funded":1,"external_id":{"isi":["000637398300002"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","project":[{"grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","call_identifier":"H2020"}],"doi":"10.1073/pnas.1920827118","acknowledged_ssus":[{"_id":"EM-Fac"}],"language":[{"iso":"eng"}],"month":"04","publication_identifier":{"eissn":["1091-6490"]},"_id":"9330","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Presynaptic α2δ subunits are key organizers of glutamatergic synapses","status":"public","ddc":["570"],"intvolume":" 118","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":2603911,"creator":"dernst","file_name":"2021_PNAS_Schoepf.pdf","access_level":"open_access","date_created":"2021-04-19T10:10:56Z","date_updated":"2021-04-19T10:10:56Z","checksum":"dd014f68ae9d7d8d8fc4139a24e04506","success":1,"relation":"main_file","file_id":"9340"}],"type":"journal_article","abstract":[{"lang":"eng","text":"In nerve cells the genes encoding for α2δ subunits of voltage-gated calcium channels have been linked to synaptic functions and neurological disease. Here we show that α2δ subunits are essential for the formation and organization of glutamatergic synapses. Using a cellular α2δ subunit triple-knockout/knockdown model, we demonstrate a failure in presynaptic differentiation evidenced by defective presynaptic calcium channel clustering and calcium influx, smaller presynaptic active zones, and a strongly reduced accumulation of presynaptic vesicle-associated proteins (synapsin and vGLUT). The presynaptic defect is associated with the downscaling of postsynaptic AMPA receptors and the postsynaptic density. The role of α2δ isoforms as synaptic organizers is highly redundant, as each individual α2δ isoform can rescue presynaptic calcium channel trafficking and expression of synaptic proteins. Moreover, α2δ-2 and α2δ-3 with mutated metal ion-dependent adhesion sites can fully rescue presynaptic synapsin expression but only partially calcium channel trafficking, suggesting that the regulatory role of α2δ subunits is independent from its role as a calcium channel subunit. Our findings influence the current view on excitatory synapse formation. First, our study suggests that postsynaptic differentiation is secondary to presynaptic differentiation. Second, the dependence of presynaptic differentiation on α2δ implicates α2δ subunits as potential nucleation points for the organization of synapses. Finally, our results suggest that α2δ subunits act as transsynaptic organizers of glutamatergic synapses, thereby aligning the synaptic active zone with the postsynaptic density."}],"issue":"14","publication":"PNAS","citation":{"ama":"Schöpf CL, Ablinger C, Geisler SM, et al. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 2021;118(14). doi:10.1073/pnas.1920827118","ista":"Schöpf CL, Ablinger C, Geisler SM, Stanika RI, Campiglio M, Kaufmann W, Nimmervoll B, Schlick B, Brockhaus J, Missler M, Shigemoto R, Obermair GJ. 2021. Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. 118(14).","ieee":"C. L. Schöpf et al., “Presynaptic α2δ subunits are key organizers of glutamatergic synapses,” PNAS, vol. 118, no. 14. National Academy of Sciences, 2021.","apa":"Schöpf, C. L., Ablinger, C., Geisler, S. M., Stanika, R. I., Campiglio, M., Kaufmann, W., … Obermair, G. J. (2021). Presynaptic α2δ subunits are key organizers of glutamatergic synapses. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1920827118","mla":"Schöpf, Clemens L., et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS, vol. 118, no. 14, National Academy of Sciences, 2021, doi:10.1073/pnas.1920827118.","short":"C.L. Schöpf, C. Ablinger, S.M. Geisler, R.I. Stanika, M. Campiglio, W. Kaufmann, B. Nimmervoll, B. Schlick, J. Brockhaus, M. Missler, R. Shigemoto, G.J. Obermair, PNAS 118 (2021).","chicago":"Schöpf, Clemens L., Cornelia Ablinger, Stefanie M. Geisler, Ruslan I. Stanika, Marta Campiglio, Walter Kaufmann, Benedikt Nimmervoll, et al. “Presynaptic Α2δ Subunits Are Key Organizers of Glutamatergic Synapses.” PNAS. National Academy of Sciences, 2021. https://doi.org/10.1073/pnas.1920827118."},"article_type":"original","date_published":"2021-04-06T00:00:00Z","scopus_import":"1","day":"06","has_accepted_license":"1","article_processing_charge":"No"}]