Mechanisms of fear learning and extinction: synaptic plasticity–fear memory connection
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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.
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.
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.
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.
KeywordsFear conditioning Extinction Synaptic transmission Synaptic plasticity Behavior Animal model
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.).
Compliance with ethical standards
Conflict of interest statement
On behalf of all authors, the corresponding author (Dr. Bolshakov) states that there is no conflict of interest.
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