Blocking of acquisition but not expression of conditioned fear-potentiated startle by NMDA antagonists in the amygdala

RECEPTORS for N-methyl-D-aspartate (NMDA) seem to have a critical role in synaptic plasticity1–4. NMDA antagonists (such as AP5) prevent induction of long-term potentiation5,6, an activity-dependent enhancement of synaptic efficacy mediated by neural mechanisms that might also underlie learning and memory. They also attenuate memory formation in several behavioural tasks7–17; there are few data, however, implicating an NMDA-sensitive measure of conditioning based on local infusion of antagonists into a brain area tightly coupled to the behavioural response used to assess conditioning. We now show that NMDA antagonists infused into the amygdala block the acquisition, but not the expression, of fear conditioning measured with a behavioural assay mediated by a defined neural circuit (fear-potentiation of the acoustic startle reflex). This effect showed anatomical and pharmacological specificity, and was not attributable to reduced salience of the stimuli of light or shock used in training. The data indicate that an NMDA-dependent process in the amygdala subserves associative fear conditioning.