THE BIOCHEMISTRY OF MEMORY FORMATION AND ITS REGULATION BY HORMONES AND NEUROMODULATORS

Recent findings have shown that the biochemistry of declarative memory in the areas of the brain involved with its formation and retrieval i s strikingly similar to that of long-term potentiation. The memory pro cess, Like long-term potentiation, involves a sequence of events that starts by the activation of glutamate receptors, is followed by a vari ety of enzymatic changes, and involves, some hours after its initiatio n, gene transcription and protein synthesis. This sequence of events t akes place in the hippocampus and, depending on the task, also in amyg dala and medial septum and, minutes later, probably in cortical areas of the brain. Peripheral hormones and a variety of brain neuromodulato ry systems may enhance or depress different steps of the biochemical s equence. The hormones act in some cases directly on the hippocampus an d amygdala (glucocorticoids), and in others (corticotropin, epinephrin e) indirectly, through reflex actions on brain neuromodulatory systems (noradrenergic, cholinergic, endorphinergic). The best studied modula tory systems are those related to stress. However, many findings demon strate a key role in memory modulation of dopaminergic synapses, of br ain benzodiazepine-like substances, and perhaps of serotonin acting at specific steps of the biochemistry of memory processes in the hippoca mpus, 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.