GABAA receptor modulation of memory: the role of endogenous benzodiazepines

GABAA receptors are known to downregulate memory consolidation processes: picrotoxin and bicuculline enhance memory, and benzodiazepines and muscimol depress it. The discovery of naturally occurring benzodiazepines in the brain prompted a recent investigation of whether these compounds could act as physiological regulators of the GABAA receptors involved in memory modulation. Different forms of learning cause a rapid reduction of benzodiazepine-like immunoreactivity in septum, amygdala and hippocampus; microinjection of the benzodiazepine antagonist flumazenil into these regions, at the time that consolidation is taking place, enhances memory. Ivan Izquierdo and Jorge Medina suggest that these and other findings indicate that benzodiazepines released in the septum, amygdala and hippocampus do indeed physiologically downregulate memory storage processes; moreover, benzodiazepine release could be modulated by the anxiety and/or stress associated with each type of learning.