Bidirectional synaptic plasticity in intercalated amygdala neurons and the extinction of conditioned fear responses

Neuroscience. 2002;115(2):455-62. doi: 10.1016/s0306-4522(02)00455-4.


Classical fear conditioning is believed to result from potentiation of conditioned synaptic inputs in the basolateral amygdala. That is, the conditioned stimulus would excite more neurons in the central nucleus and, via their projections to the brainstem and hypothalamus, evoke fear responses. However, much data suggests that extinction of fear responses does not depend on the reversal of these changes but on a parallel NMDA-dependent learning that competes with the first one. Because they control impulse traffic from the basolateral amygdala to the central nucleus, GABAergic neurons of the intercalated cell masses are ideally located to implement this second learning. Consistent with this hypothesis, the present study shows that low- and high-frequency stimulation of basolateral afferents respectively induce long-term depression (LTD) and potentiation (LTP) of responses in intercalated cells. Moreover, induction of LTP and LTD is prevented by application of an NMDA antagonist. To determine how these activity-dependent changes are expressed, we tested whether LTD and LTP induction are associated with modifications in paired-pulse facilitation, an index of transmitter release probability. Only LTP induction was associated with a change in paired-pulse facilitation. Depotentiation of previously potentiated synapses did not revert the modification in paired pulse facilitation, suggesting that LTP is associated with presynaptic alterations, but that LTD and depotentiation depend on postsynaptic changes. Taken together, our results suggest that basolateral synapses onto intercalated neurons can express NMDA-dependent LTP and LTD, consistent with the possibility that intercalated neurons are a critical locus of plasticity for the extinction of conditioned fear responses. Ultimately, these plastic events may prevent conditioned amygdala responses from exciting neurons of the central nucleus, and thus from evoking conditioned fear responses.

Publication types

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

MeSH terms

  • Amygdala / cytology*
  • Amygdala / physiology*
  • Animals
  • Conditioning, Psychological / physiology
  • Electric Stimulation
  • Excitatory Postsynaptic Potentials / physiology
  • Extinction, Psychological / physiology
  • Fear / physiology*
  • Guinea Pigs
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / physiology
  • Membrane Potentials / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Receptors, N-Methyl-D-Aspartate / physiology


  • Receptors, N-Methyl-D-Aspartate