Serotonergic mechanisms of memory trace retrieval.

This review summarizes our research examining the role of serotonergic mechanisms in memory processes. Analysis of serotonin (5-HT) metabolism and specific binding of radioligand [(3)H]5-HT in various brain structures at different stages of a conditioned passive avoidance response in rats has demonstrated that 5-HT is involved in the processes of memory retrieval rather than in acquisition. The process of retrieving a conditioned response formed to a new conditioned stimulus is accompanied by a reduction in postsynaptic 5-HT receptor binding in the amygdala, periacqueductal gray matter, and striatum, while no changes have been seen in the hippocampus or prefrontal cortex. The changes in 5-HT activity found in the amygdala and periacqueductal gray matter indicate that 5-HT is involved in the emotional mechanisms activating a memory trace. The animals that due to developed amnesia had impaired memory trace retrieval showed no decreases in 5-HT receptor binding in either the emotional areas of the brain or the striatum. Furthermore, a memory retrieval deficit evoked by presentation of a habituated conditioned stimulus (latent inhibition) resulted in an enhanced 5-HT activity in these structures. From these data it appears that a reduction in postsynaptic 5-HT receptor binding in such brain structures as the amygdala and periacqueductal gray matter is necessary for memory trace retrieval relating to an aversive event. Without this, the emotional mechanisms of reinforcement of conditioned stimulus are not triggered and extraction of a corresponding engram does not occur.