Memory formation, amnesia, improved memory and reversed amnesia: 5-HT role

Traditionally, the search for memory circuits has been focused on examinations of amnesic and AD patients, cerebral lesions and neuroimaging. A complementary alternative has become the use of autoradiography with radioligands, aiming to identify neurobiological markers associated with memory formation, amnesia states and (more recently) recovery from memory deficits. Indeed, ex vivo autoradiographic studies offer the advantage of detecting functionally active receptors altered by pharmacological tools during memory formation, amnesia states and memory recovery. Moreover, serotonin (5-hydroxytryptamine, 5-HT) systems have become a pharmacological and genetic target in the treatment of memory disorders. Herein evidence from studies involving expression of 5-HT1A, 5-HT2A, 5-HT4, and 5-HT6 receptors in memory formation, amnesia conditions (e.g., pharmacological models or aging) and recovery of memory is reviewed. Thus, specific 5-HT receptors were expressed in trained animals relative to untrained in brain areas such as cortex, hippocampus and amygdala. However, relative to the control group, rats showing amnesia or recovered memory, showed in the hippocampus, region where explicit memory is formed, a complex pattern of 5-HT receptor expression. An intermediate expression occurred in amygdala, septum and some cortical areas in charge of explicit memory storage. Even in brain areas thought to be in charge of procedural memory such as basal ganglia, animals showing recovered memory displayed an intermediate expression, while amnesic groups, depending on the pharmacological amnesia model, showed up- or down-regulation. In conclusion, evidence indicates that autoradiography, by using specific radioligands, offers excellent opportunities to map dynamic changes in brain areas engaged in these cognitive processes. The 5-HT modulatory role strengthens or suppresses memory is critically depend on the timing of the memory formation.