Fear-Potentiated Startle as a Model System for Analyzing Learning and Memory

Previous research has shown that the acoustic startle response, a simple reflex mediated by four synapses in the brainstem and spinal cord, can be increased when elicited in the presence of a light previously paired with a footshock. This fear-potentiated startle effect can be selectively blocked by drugs that decrease anxiety in humans as well as by lesions of the central nucleus of the amygdala, an area of the brain known to be critical for fear. This year we found that local infusion of N-methyl-D-aspartate NMDA selective antagonists such as AP5 or CPP completely block the acquisition of fear- potentiated startle. This effect could not be attributed to a decrease in shock sensitivity or vision and did not occur when these compounds were infused into the cerebellum. These data indicate that an NMDA-dependent mechanism in the amygdala is involved in fear conditioning and that fear-potentiated startle may provide an excellent behavioral model system to analyze cellular and biochemical mechanisms of learning and memory.