Protein kinase C-gamma knockout mice show impaired hippocampal short-term memory while preserved long-term memory

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• dc.contributor.author Gomis González, Maria, 1988-
• dc.contributor.author Galera López, Lorena, 1993-
• dc.contributor.author Ten-Blanco, Marc
• dc.contributor.author Busquets Garcia, Arnau, 1985-
• dc.contributor.author Cox, Thomas
• dc.contributor.author Maldonado, Rafael, 1961-
• dc.contributor.author Ozaita Mintegui, Andrés, 1969-
• dc.date.accessioned 2020-10-01T06:22:38Z
• dc.date.issued 2020
• dc.description.abstract The brain encodes, stores, and retrieves relevant information in the form of memories that are classified as short-term (STM) and long-term memories (LTM) depending on the interval between acquisition and retrieval. It is classically accepted that STM undergo a consolidation process to form LTM, but the molecular determinants involved are not well understood. Among the molecular components relevant for memory formation, we focused our attention on the protein kinase C (PKC) family of enzymes since they control key aspects of the synaptic plasticity and memory. Within the different PKC isoforms, PKC-gamma has been specifically associated with learning and memory since mice lacking this isoform (PKC-gamma KO mice) showed mild cognitive impairment and deficits in hippocampal synaptic plasticity. We now reveal that PKC-gamma KO mice present a severe impairment in hippocampal-dependent STM using different memory tests including the novel object-recognition and novel place-recognition, context fear conditioning and trace fear conditioning. In contrast, no differences between genotypes were observed in an amygdala-dependent test, the delay fear conditioning. Strikingly, all LTM tasks that could be assessed 24 h after acquisition were not perturbed in the KO mice. The analysis of c-Fos expression in several brain areas after trace fear conditioning acquisition showed a blunted response in the dentate gyrus of PKC-gamma KO mice compared with WT mice, but such differences between genotypes were absent when the amygdala or the prefrontal cortex were examined. In the hippocampus, PKC-gamma was found to translocate to the membrane after auditory trace, but not after delay fear conditioning. Together, these results indicate that PKC-gamma dysfunction affects specifically hippocampal-dependent STM performance and disclose PKC-gamma as a molecular player differentially involved in STM and LTM processes.
• dc.description.sponsorship This work was supported by the Ministerio de Economía, Innovación y Competitividad (MINECO) [#BFU2015-68568-P to A.O., #SAF2017-84060-R to R.M.]; the Instituto de Salud Carlos III [#RD16/0017/0020 to R.M.]; the Ministerio de Ciencia, Innovación y Universidades [# RTI2018-099282-B-I00 (AEI/FEDER/UE) to A.O.]; the Generalitat de Catalunya [2017SGR-669 to R.M.]; the ICREA (Institució Catalana de Recerca i Estudis Avançats) Academia to A.O. and R.M.; Grant “Unidad de Excelencia María de Maeztu,” funded by the MINECO [#MDM-2014-0370]; PLAN E (Plan Español para el Estímulo de la Economía y el Empleo). FEDER funding is also acknowledged.
• dc.format.mimetype application/pdf
• dc.identifier.citation Gomis-González M, Galera-López L, Ten-Blanco M, Busquets-Garcia A, Cox T, Maldonado R, Ozaita A. Protein kinase C-gamma knockout mice show impaired hippocampal short-term memory while preserved long-term memory. Mol Neurobiol. 2021;58(2):617-30. DOI: 10.1007/s12035-020-02135-6
• dc.identifier.doi http://dx.doi.org/10.1007/s12035-020-02135-6
• dc.identifier.issn 0893-7648
• dc.identifier.uri http://hdl.handle.net/10230/45360
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Mol Neurobiol. 2021 Feb;58(2):617-630
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68568-P
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/SAF2017-84060-R
• dc.rights © Springer The final publication is available at Springer via http://dx.doi.org/10.1007/s12035-020-02135-6.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Short-term memory
• dc.subject.keyword Long-term memory
• dc.subject.keyword PKC-gamma
• dc.subject.keyword Memory acquisition
• dc.subject.keyword c-Fos expression
• dc.title Protein kinase C-gamma knockout mice show impaired hippocampal short-term memory while preserved long-term memory
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion