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

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 to 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.

KIBRA-PKCγ signaling pathway modulates memory performance in mice and humans

“…Inhibition of PKCγ significantly impaired GluA2 S880 and GluA1 S831 phosphorylation, even at the saturating level of 2 μM PMA treatment. Consistent with the important role of PKCγ in modulating synaptic plasticity, learning, and memory 33–36 , these results combined indicate that PKCγ phosphorylates AMPARs and KIBRA can facilitate its interaction with AMPARs.…”

Peripheral CB1 receptor blockade acts as a memory enhancer through an adrenergic-dependent mechanism

“…The Novel object recognition test (NORT) was performed following a protocol previously described (Gomis-González et al, 2021).…”

A low repeated dose of Δ9-tetrahydrocannabinol affects memory performance through serotonergic signalling in mice

“…The novel object recognition (NOR) memory test is a behavioural task used to measure non-emotional declarative memory in mice. NOR test was performed as described before (Gomis-González et al , 2021) in a V-shaped maze (V-maze). On day 1, mice were habituated to the empty V-maze for 9 min (habituation phase).…”

“…Spatial learning and memory was assessed using the Barnes maze, as previously described (Gomis-González et al , 2021). The maze consists of a circular platform (90 cm in diameter) with 20 equally spaced holes through which mice may escape from a bright light (300 lx).…”