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Mechanisms of fear learning and extinction: synaptic plasticity–fear memory connection

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Abstract

Rationale

The ability to memorize threat-associated cues and subsequently react to them, exhibiting escape or avoidance responses, is an essential, often life-saving behavioral mechanism that can be experimentally studied using the fear (threat) conditioning training paradigm. Presently, there is substantial evidence supporting the Synaptic Plasticity–Memory (SPM) hypothesis in relation to the mechanisms underlying the acquisition, retention, and extinction of conditioned fear memory.

Objectives

The purpose of this review article is to summarize findings supporting the SPM hypothesis in the context of conditioned fear control, applying the set of criteria and tests which were proposed as necessary to causally link lasting changes in synaptic transmission in corresponding neural circuits to fear memory acquisition and extinction with an emphasis on their pharmacological diversity.

Results

The mechanisms of synaptic plasticity in fear circuits exhibit complex pharmacological profiles and satisfy all four SPM criteria—detectability, anterograde alteration, retrograde alteration, and mimicry.

Conclusion

The reviewed findings, accumulated over the last two decades, provide support for both necessity and sufficiency of synaptic plasticity in fear circuits for fear memory acquisition and retention, and, in part, for fear extinction, with the latter requiring additional experimental work.

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Acknowledgments

We thank Vernon Clarke and members of the laboratory for help and constructive discussions. This work was supported by grants R01MH108665 and R01MH105851 from the NIMH (to V.Y.B.) and The Phyllis & Jerome Lyle Rappaport Foundation (to N.V.L.).

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  1. Department of Psychiatry, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA

    Natalia V. Luchkina & Vadim Y. Bolshakov

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  1. Natalia V. Luchkina
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Correspondence to Natalia V. Luchkina or Vadim Y. Bolshakov.

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This article belongs to a Special Issue on Psychopharmacology of Extinction

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Luchkina, N.V., Bolshakov, V.Y. Mechanisms of fear learning and extinction: synaptic plasticity–fear memory connection. Psychopharmacology 236, 163–182 (2019). https://doi.org/10.1007/s00213-018-5104-4

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