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Protein Kinase C-Gamma Knockout Mice Show Impaired Hippocampal Short-Term Memory While Preserved Long-Term Memory

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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.

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Acknowledgments

We thank Dulce Real and Francisco Porrón for expert technical assistance and the Laboratory of Neuropharmacology-NeuroPhar for helpful discussion. Predoctoral fellowship by FPI (MINEICO/FEDER, EU) (LG-L). Predoctoral fellowship from the Spanish Ministry of Education (AB-G).

Funding

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.

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Author notes

  1. Maria Gomis-González & Arnau Busquets-Garcia

    Present address: Integrative Pharmacology and Systems Neuroscience Research Group, Hospital del Mar Medical Research Institute, 08003, Barcelona, Spain

  2. Marc Ten-Blanco

    Present address: Faculty of Experimental Sciences, Universidad Francisco de Vitoria, UFV, 28223, Pozuelo de Alarcón, Spain

  3. Thomas Cox

    Present address: Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, GU2 7WG, Guildford, UK

  4. Maria Gomis-González and Lorena Galera-López contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Pompeu Fabra University, 08003, Barcelona, Spain

    Maria Gomis-González, Lorena Galera-López, Marc Ten-Blanco, Arnau Busquets-Garcia, Thomas Cox, Rafael Maldonado & Andrés Ozaita

  2. IMIM, Hospital del Mar Medical Research Institute, Barcelona, Spain

    Rafael Maldonado & Andrés Ozaita

  3. Laboratori de Neurofarmacologia, Facultat de Ciències de la Salut i de la Vida, Universitat Pompeu Fabra, Parc de Recerca Biomèdica de Barcelona, C/ Doctor Aiguader 88, 08003, Barcelona, Spain

    Rafael Maldonado & Andrés Ozaita

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Gomis-González, M., Galera-López, L., Ten-Blanco, M. et al. Protein Kinase C-Gamma Knockout Mice Show Impaired Hippocampal Short-Term Memory While Preserved Long-Term Memory. Mol Neurobiol 58, 617–630 (2021). https://doi.org/10.1007/s12035-020-02135-6

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