Elsevier

Neuropharmacology

Volume 52, Issue 1, January 2007, Pages 215-227
Neuropharmacology

Long-term potentiation in the amygdala: A cellular mechanism of fear learning and memory

https://doi.org/10.1016/j.neuropharm.2006.06.022Get rights and content

Abstract

Much of the research on long-term potentiation (LTP) is motivated by the question of whether changes in synaptic strength similar to LTP underlie learning and memory. Here we discuss findings from studies on fear conditioning, a form of associative learning whose neural circuitry is relatively well understood, that may be particularly suited for addressing this question. We first review the evidence suggesting that fear conditioning is mediated by changes in synaptic strength at sensory inputs to the lateral nucleus of the amygdala. We then discuss several outstanding questions that will be important for future research on the role of synaptic plasticity in fear learning. The results gained from these studies may shed light not only on fear conditioning, but may also help unravel more general cellular mechanisms of learning and memory.

Section snippets

Introduction: A cellular hypothesis of fear conditioning

Long-term potentiation (LTP) has received a tremendous amount of attention in the roughly 30 years since it was first described by Bliss and Lomo (1973). This interest has been fueled to a large degree by the widely held hypothesis that learning and memory is mediated by changes in the strength of synapses in neural circuits. According to this hypothesis, neural activity during learning gives rise to long-term changes in synaptic strength, which allows memories to be stored and later retrieved (

CS-evoked responses in the LA increase during fear conditioning

If fear conditioning is mediated by an increase in the strength of synapses that carry auditory (CS) information to the LA, one would expect to observe an enhancement in the responses of LA neurons to a CS during the course of fear learning. To date, this prediction has been confirmed by a number of studies that have recorded either field potential or single-unit responses in the LA during fear conditioning (Quirk et al., 1995, Rogan et al., 1997, Collins and Pare, 2000, Repa et al., 2001,

Outstanding questions for future research

Although considerable progress has been made in relating synaptic plasticity in the amygdala to fear learning and memory, several questions concerning this relationship remain unanswered. Below we discuss three research questions that may advance our understanding of how plasticity in the LA contributes to fear conditioning in the coming years. This list is not meant to be exhaustive, but rather to highlight a few important outstanding questions.

Conclusion

Considerable progress has been made in relating activity-dependent changes in synaptic strength to learning and memory since Bliss and Lomo first described LTP in 1973. We have argued that studies linking fear conditioning to LTP in the amygdala constitute an important part of this progress. The findings reviewed here strongly suggest that LTP-like synaptic changes occur as a result of fear learning, and that such changes are necessary for fear memories to be formed. Nevertheless, our

Acknowledgments

This work was supported by NIH Grants R01 MH46516, R37 MH38774, K05 MH067048, and P50 MH58911 to J.E.L., an NIMH NRSA MH077458 to C.K.C. and CNRS-PICS to V.D.

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