Neural Mechanisms of Extinction Learning and Retrieval

Abstract

Emotional learning is necessary for individuals to survive and prosper. Once acquired, however, emotional associations are not always expressed. Indeed, the regulation of emotional expression under varying environmental conditions is essential for mental health. The simplest form of emotional regulation is extinction, in which conditioned responding to a stimulus decreases when the reinforcer is omitted. Two decades of research on the neural mechanisms of fear conditioning have laid the groundwork for understanding extinction. In this review, we summarize recent work on the neural mechanisms of extinction learning. Like other forms of learning, extinction occurs in three phases: acquisition, consolidation, and retrieval, each of which depends on specific structures (amygdala, prefrontal cortex, hippocampus) and molecular mechanisms (receptors and signaling pathways). Pharmacological methods to facilitate consolidation and retrieval of extinction, for both aversive and appetitive conditioning, are setting the stage for novel treatments for anxiety disorders and addictions.

Infralimbic cortex controls the activity of the hypothalamus–pituitary–adrenal axis and the formation of aversive memory: Effects of environmental enrichment

“…These results together with the fact that the stimulation of prelimbic cortex inhibits the acquisition of aversive memory [8] support the idea of an opposite role of prelimbic and infralimbic cortices in emotional processing [35]. Our results are in agreement with studies in which infralimbic lesions reduced the retention latency using the same behavioural paradigm [13].…”

The brain-specific microRNA miR-128b regulates the formation of fear-extinction memory

“…Fear extinction, the gradual reduction in the fear response by repeated presentation of non-reinforced fear-related cues, is an important inhibitory learning process that generates a new memory, which is necessary for overcoming conditioned fear 1 . The initial phase of extinction learning involves retrieval and expression of the original fear memory, which naturally permits either restabilization of the original trace or new extinction learning.…”

“…The initial phase of extinction learning involves retrieval and expression of the original fear memory, which naturally permits either restabilization of the original trace or new extinction learning. Although there is evidence to suggest that the acquisition of conditioned fear and the encoding of fear extinction share some common molecular substrates 1 , the function of genes expressed at the time of retrieval of fear memory and how they are regulated to allow fear extinction to proceed has not been thoroughly investigated. MicroRNAs are a family of small non-coding RNAs that regulate gene function by inhibiting the expression of their target mRNAs [2][3] , and recent findings implicate microRNA activity in learning associated with cocaine and nicotine addiction 4-5 , as well as suggesting a more general role for miR-124, -132 and -134 in hippocampaldependent learning and memory [6][7][8] .…”

Computational models of reinforcement learning: the role of dopamine as a reward signal

“…Other related examples of extinction and renewal have been modeled in basal ganglia networks to account for the effects of dopaminergic pharmacological agents on the development and extinction of motor behaviors in rats (Wiecki et al 2009). Finally, fear conditioning is another well documented conditioning paradigm amenable to extinction studies (reviewed in Ehrlich et al 2009;Quirk and Mueller 2007). The computational role of dopamine in this paradigm is however still unclear.…”