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

Gomis González, Maria, 1988-; Galera López, Lorena, 1993-; Ten-Blanco, Marc; Busquets Garcia, Arnau, 1985-; Cox, Thomas; Maldonado, Rafael, 1961-; Ozaita Mintegui, Andrés, 1969-

doi:http://dx.doi.org/10.1007/s12035-020-02135-6

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

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

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.