Effects of anisomycin infusions into the dorsal striatum on memory consolidation of intense training and neurotransmitter activity

摘要

The most influential hypothesis about the neurobiological basis of memory consolidation posits that this process is dependent upon de novo protein synthesis. Strong support for this proposition has been provided by a multitude of experiments showing that protein synthesis inhibitors (PSIs) interfere with consolidation. However, this hypothesis has been challenged by the results of studies showing that PSIs also produce a host of side effects that, by themselves, could account for their amnestic effects. It has been demonstrated that amnestic treatments become innocuous when administered to animals that have been subjected to intense training in a variety of learning tasks. We now report that while infusion of anisomycin (ANI), a PSI, into the dorsal striatum (DS) impairs memory consolidation of inhibitory avoidance learning in response to moderate aversive stimuli, such impairment by ANI is overcome by application of an intense stimulus. We also confirmed that ANI induces inhibition of protein synthesis in the DS, as evidenced by a reduction of the activity-regulated cytoskeletal associated protein (Arc). We found, for the first time, that ANI also induces an increased concentration of serotonin in the DS, which, by itself, may account for the interference with memory consolidation. These findings suggest that de novo protein synthesis in the dorsal striatum is not necessary for the consolidation of intense emotionally arousing experiences. The possibility of a non-genomic-dependent mechanism of memory consolidation is discussed.