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

• Published in: Molecular neurobiology 2021-02, Vol.58 (2), p.617-630
• Main Authors: Gomis-González, Maria, Galera-López, Lorena, Ten-Blanco, Marc, Busquets-Garcia, Arnau, Cox, Thomas, Maldonado, Rafael, Ozaita, Andrés
• Format: Article
• Language: English
• Subjects: Amygdala; Animals; Biomedical and Life Sciences; Biomedicine; c-Fos protein; Cell Biology; Cognitive ability; Conditioning, Classical; Dentate gyrus; Dentate Gyrus - pathology; Fear; Fear conditioning; Genotypes; Hippocampal plasticity; Hippocampus; Hippocampus - enzymology; Isoenzymes - metabolism; Isoforms; Kinases; Long term memory; Male; Memory; Memory, Long-Term; Memory, Short-Term; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurobiology; Neurology; Neurosciences; Prefrontal cortex; Protein kinase C; Protein Kinase C - deficiency; Protein Kinase C - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Rodents; Short term memory; Spatial Memory; Synaptic plasticity
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-020-02135-6

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.