The biochemistry of memory formation and its regulation by hormones and neuromodulators

Abstract

Recent findings have shown that the biochemistry of declarative memory in the areas of the brain involved with its formation and retrieval is strikingly similar to that of long-term potentiation. The memory process, like long-term potentiation, involves a sequence of events that starts by the activation of glutamate receptors, is followed by a variety of enzymatic changes, and involves, some hours after its initiation, gene transcription and protein synthesis. This sequence of events takes place in the hippocampus and, depending on the task, also in amygdala and medial septum and, minutes later, probably in cortical areas of the brain. Peripheral hormones and a variety of brain neuromodulatory systems may enhance or depress different steps of the biochemical sequence. The hormones act in some cases directly on the hippocampus and amygdala (glucocorticoids), and in others (corticotropin, epinephrine) indirectly, through reflex actions on brain neuromodulatory systems (noradrenergic, cholinergic, endorphinergic). The best studied modulatory systems are those related to stress. However, many findings demonstrate a key role in memory modulation of dopaminergic synapses, of brain benzodiazepine-like substances, and perhaps of serotonin acting at specific steps of the biochemistry of memory processes in the hippocampus, amygdala, or elsewhere. Since these systems are involved in the regulation of anxiety and mood, the findings suggest a strong relation between anxiety, mood, and memory, both in normal and in pathological conditions.