anisomycin and clasto-lactacystin-beta-lactone

Topics: Amygdala; Animals; Anisomycin; CA1 Region, Hippocampal; Clonidine; Cognition; Cysteine Proteinase Inhibitors; Early Growth Response Protein 1; Excitatory Amino Acid Antagonists; Fear; GABA-A Receptor Agonists; Lactones; Memory; Midline Thalamic Nuclei; Muscimol; Neurons; Piperidines; Prefrontal Cortex; Rats; Receptors, N-Methyl-D-Aspartate

Numerous studies have indicated that the consolidation of contextual fear memories supported by an aversive outcome like footshock requires de novo protein synthesis as well as protein degradation mediated by the ubiquitin-proteasome system (UPS). Context memory formed in the absence of an aversive stimulus by simple exposure to a novel environment requires de novo protein synthesis in both the dorsal (dHPC) and ventral (vHPC) hippocampus. However, the role of UPS-mediated protein degradation in the consolidation of context memory in the absence of a strong aversive stimulus has not been investigated. In the present study, we used the context preexposure facilitation effect (CPFE) procedure, which allows for the dissociation of context learning from context-shock learning, to investigate the role of activity-dependent protein degradation in the dHPC and vHPC during the formation of a context memory. We report that blocking protein degradation with the proteasome inhibitor clasto-lactacystin β-lactone (βLac) or blocking protein synthesis with anisomycin (ANI) immediately after context preexposure significantly impaired context memory formation. Additionally, we examined 20S proteasome activity at different time points following context exposure and saw that the activity of proteasomes in the dHPC increases immediately after stimulus exposure while the vHPC exhibits a biphasic pattern of proteolytic activity. Taken together, these data suggest that the requirement of increased proteolysis during memory consolidation is not driven by processes triggered by the strong aversive outcome (i.e., shock) normally used to support fear conditioning.

Topics: Analysis of Variance; Animals; Anisomycin; Conditioning, Classical; Cysteine Proteinase Inhibitors; Fear; Freezing Reaction, Cataleptic; Hippocampus; Lactones; Male; Memory; Proteasome Endopeptidase Complex; Protein Synthesis Inhibitors; Proteolysis; Rats; Rats, Long-Evans; Synaptosomes; Time Factors

Memories are dynamic, rather than static, in nature. The reactivation of a memory through re-exposure to salient training stimuli results in its destabilization, necessitating a restabilization process known as reconsolidation, a disruption of which leads to amnesia. I found that one normal function of hippocampal memory reconsolidation in rats is to modify the strength of a contextual-fear memory as a result of further learning.

Topics: Amnesia; Analysis of Variance; Animals; Anisomycin; Behavior, Animal; Brain-Derived Neurotrophic Factor; Conditioning, Psychological; Early Growth Response Protein 1; Fear; Freezing Reaction, Cataleptic; Hippocampus; Lactones; Learning; Male; Memory; Oligodeoxyribonucleotides, Antisense; Protein Synthesis Inhibitors; Rats

Reactivated memory undergoes a rebuilding process that depends on de novo protein synthesis. This suggests that retrieval is dynamic and serves to incorporate new information into preexisting memories. However, little is known about whether or not protein degradation is involved in the reorganization of retrieved memory. We found that postsynaptic proteins were degraded in the hippocampus by polyubiquitination after retrieval of contextual fear memory. Moreover, the infusion of proteasome inhibitor into the CA1 region immediately after retrieval prevented anisomycin-induced memory impairment, as well as the extinction of fear memory. This suggests that ubiquitin- and proteasome-dependent protein degradation underlies destabilization processes after fear memory retrieval. It also provides strong evidence for the existence of reorganization processes whereby preexisting memory is disrupted by protein degradation, and updated memory is reconsolidated by protein synthesis.

Topics: Animals; Anisomycin; Conditioning, Psychological; Extinction, Psychological; Fear; Hippocampus; Lactones; Male; Memory; Mental Recall; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Proteasome Endopeptidase Complex; Protein Synthesis Inhibitors; Synapses; Ubiquitination