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

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.