NMDA receptors are essential for the acquisition, but not expression, of conditional fear and associative spike firing in the lateral amygdala

Eur J Neurosci. 2004 Jul;20(2):537-48. doi: 10.1111/j.1460-9568.2004.03513.x.


We examined the contribution of N-methyl-D-aspartate (NMDA) receptors (NMDARs) to the acquisition and expression of amygdaloid plasticity and Pavlovian fear conditioning using single-unit recording techniques in behaving rats. We demonstrate that NMDARs are essential for the acquisition of both behavioral and neuronal correlates of conditional fear, but play a comparatively limited role in their expression. Administration of the competitive NMDAR antagonist +/--3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP) prior to auditory fear conditioning completely abolished the acquisition of conditional freezing and conditional single-unit activity in the lateral amygdala (LA). In contrast, CPP given prior to extinction testing did not affect the expression of conditional single-unit activity in LA, despite producing deficits in conditional freezing. Administration of CPP also blocked the induction of long-term potentiation in the amygdala. Together, these data suggest that NMDARs are essential for the acquisition of conditioning-related plasticity in the amygdala, and that NMDARs are more critical for regulating synaptic plasticity and learning than routine synaptic transmission in the circuitry supporting fear conditioning.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Amygdala / drug effects
  • Amygdala / physiology*
  • Animals
  • Behavior, Animal
  • Conditioning, Psychological / drug effects
  • Conditioning, Psychological / physiology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fear / physiology*
  • Male
  • Piperazines / pharmacology
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Time Factors


  • Excitatory Amino Acid Antagonists
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid