Hippocampal protein kinase C family members in spatial memory retrieval in the mouse.

Although a few individual members of the protein kinase C (PKC) family were studied in spatial memory no systematic approach was carried out to concomitantly determine all described PKC family members in spatial memory of the mouse. It was therefore the aim of the current study to link hippocampal PKCs to memory retrieval in the Morris water maze (MWM). CD1 mice were trained (n=9) or untrained (n=9) in the MWM, hippocampi were taken 6h following the test for memory retrieval and PKCs were determined in mouse hippocampi by immunoblotting.

Distinct set of kinases induced after retrieval of spatial memory discriminate memory modulation processes in the mouse hippocampus.

Protein phosphorylation and dephosphorylation events play a key role in memory formation and various protein kinases and phosphatases have been firmly associated with memory performance. Here, we determined expression changes of protein kinases and phosphatases following retrieval of spatial memory in CD1 mice in a Morris Water Maze task, using antibody microarrays and confirmatory Western blot. Comparing changes following single and consecutive retrieval, we identified stably and differentially expressed kinases, some of which have never been implicated before in memory functions.

Strain-dependent hippocampal protein levels of GABA(B)-receptor subunit 2 and NMDA-receptor subunit 1.

Mouse strains differ from one another in cognitive function as learning and memory as well as synaptic plasticity. Although molecular explanations for this heterogeneity have been proposed, there is no available information on strain-dependent GABA(B)-receptor levels in hippocampus that may explain observed differences in GABA(B)-receptor-mediated cognitive enhancement among strains. This formed the rationale to perform a study on GABA(B) and related somatostatin receptor 5 and NMDA receptors that have been reported to be involved in memory enhancement by GABA(B)-antagonism.

Cognitive enhancement by SGS742 in OF1 mice is linked to specific hippocampal protein expression.

Cognitive enhancement by the GABA (B) antagonist SGS742 has been reported and we decided to search for proteins involved. Hippocampi from OF1 mice were from SGS742- treated animals and three control groups. Proteins were extracted and run on 2DE, and spots were quantified.

Hippocampal synapsin isoform levels are linked to spatial memory enhancement by SGS742.

Synapsins are essential proteins for synaptic plasticity and there is no information available for their role in cognitive enhancement (CE) of spatial memory formation. It was therefore the aim of the study to link individual synapsin proteins and their isoforms to spatial memory formation enhanced by SGS742 in the mouse. Extracted hippocampal proteins from a cognitive study treating OF1 mice with the cognitive enhancer SGS742 and tested in the Morris water maze, were run on two-dimensional gel electrophoresis.

Evaluation of spatial memory of C57BL/6J and CD1 mice in the Barnes maze, the Multiple T-maze and in the Morris water maze.

Evaluation of spatial learning and memory is mainly carried out using the Morris water maze as a single paradigm. We intended to test whether mice in the Barnes maze and Multiple T-maze would lead to comparable results and to test two individual mouse strains with different anxiety levels. C57BL/6J and CD1 male mice were used in the experiments.

Hippocampal levels of phosphorylated protein kinase A (phosphor-S96) are linked to spatial memory enhancement by SGS742.

Cognitive enhancement by the GABA (B) receptor antagonist SGS742 has been well-documented, but mechanisms of action are not fully elucidated. Previous work has proposed involvement of somatostatin-14 and protein kinase C in cognitive enhancement; phospho-protein kinase A (p-PKA), fyn, and phospho-fyn are known signaling systems for spatial memory. It was the aim of the study to determine hippocampal levels of these proteins following SGS742-treatment and to correlate them with the outcome from the Morris water maze (MWM), represented by the parameter "time spent in the target quadrant" during the probe trial.

The role of post-translational modifications for learning and memory formation.

Learning and memory depend on molecular mechanisms involving the protein machinery. Recent evidence proposes that post-translational modifications (PTMs) play a major role in these cognitive processes. PTMs including phosphorylation of serine, threonine, and tyrosine are already well-documented to play a role for synaptic plasticity of the brain, neurotransmitter release, vesicle trafficking and synaptosomal or synaptosomal-associated proteins are substrates of a series of specific protein kinases and their counterparts, protein phosphatases.

The cognitive enhancer SGS742 does not involve major known signaling cascades in OF1 mice.

In a previous study we have shown that SGS742, a cognitive enhancer acting by GABA(B) receptor antagonism improved spatial learning in OF1 mice. The aim of the study was therefore to screen representatives of several signaling cascades known to be involved in memory formation at the protein level. NaCl-, SGS742- treatment and yoked controls for NaCl and SGS742 were studied.

Apodemus sylvaticus (LOXT) is a suitable mouse strain for testing spatial memory retention in the Morris water maze.

Information on the difference in cognitive function between laboratory and wild-caught mice is anecdotal and this question has not been systematically studied. Moreover, studying a wild-caught mouse strain per se may add information to the repertoire of mouse strains available. We aimed to study spatial memory in a wild mouse strain (Apodemus sylvaticus, AS) as compared to two individual laboratory mouse strains.

Strain-dependent effects of SGS742 in the mouse.

SGS742 has been reported to increase spatial memory in rodents. However, effects of SGS742 have not been systematically assessed in different strains so far and indeed strains show different cognitive abilities per se. The aim of the study was therefore to examine the effect of SGS742 in three different inbred (C57BL/6J, DBA/2, BALB/c) strains and three outbred strains (CD1, CF1, OF1).