Extinction of emotional learning: Contribution of medial prefrontal cortex

Morgan, Maria A.; Romanski, Lizabeth M.; LeDoux, Joseph E.

doi:10.1016/0304-3940(93)90241-c

Cited by 820 publications

(619 citation statements)

References 23 publications

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“…Among these regions, the medial prefrontal cortex (mPFC) has extensive bidirectional connections with the hippocampus and amygdala, which supports a role of this structure on mnesic processes (Goldman-Rakic et al, 1984;von Hoesen et al, 1972von Hoesen et al, , 1975. Thus, the medial part has been proposed to participate in short-term object memory in rats and monkeys (Kowalska et al, 1991), and the lesion of this region is also known to interfere with the extinction of cued conditioned fear responses (Morgan et al, 1993;Morgan and LeDoux, 1995;Quirk et al, 2000), although negative results have also been reported (Gewirtz et al, 1997). The role of the mPFC in contextual conditioned fear, a type of memory that is dependent on both hippocampal and amygdala function, has been little explored, and it is known that prefrontocortical lesions do not affect acquisition and extinction of contextual conditioned fear (Morgan et al, 1993).…”

Section: Introductionmentioning

confidence: 91%

“…Thus, the medial part has been proposed to participate in short-term object memory in rats and monkeys (Kowalska et al, 1991), and the lesion of this region is also known to interfere with the extinction of cued conditioned fear responses (Morgan et al, 1993;Morgan and LeDoux, 1995;Quirk et al, 2000), although negative results have also been reported (Gewirtz et al, 1997). The role of the mPFC in contextual conditioned fear, a type of memory that is dependent on both hippocampal and amygdala function, has been little explored, and it is known that prefrontocortical lesions do not affect acquisition and extinction of contextual conditioned fear (Morgan et al, 1993). The mPFC has also been involved in social interaction, because medial prefrontal transection is known to enhance social interaction in rats Tucci et al, 2000), but its role on mnesic processes during social interaction is not known.…”

Section: Introductionmentioning

confidence: 99%

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Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory

Fernández-Espejo

2002

Neuropsychopharmacol

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Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short-and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (476%) led to a reactive enhancement of accumbal dopamine content (po0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (476%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short-term social interaction memory.

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Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory

Fernández-Espejo

2002

Neuropsychopharmacol

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“…72,137,147 Surprisingly, in contrast to these findings, lesion or inactivation studies examining the involvement of mPFC in extinction have been inconsistent. Some investigators have reported an impairment of extinction of conditioned freezing following electrolytic lesions of mPFC or, more specifically, IL, in rodents [148][149][150][151] but there also have been some notable failures to obtain a PFC lesion effect 119,121,152,153 as well as mixed findings. 154 It is possible that the timing of the lesion with respect to fear acquisition is significant since the reports of positive lesion effects all involve lesions induced before fear conditioning, suggesting that the apparent extinction effect may in fact be a secondary effect on acquisition.…”

Section: Neural Mechanismsmentioning

confidence: 99%

Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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“…Thus, our data are consistent with a neural model for fear extinction that involves a distributed network, where the lateral amygdala plays a central role. Other likely candidate sites are the medial prefrontal cortex (Morgan et al, 1993;Quirk et al, 2000;Milad and Quirk, 2002;Santini et al, 2004), the periaqueductal gray matter (McNally et al, 2004), and the hippocampus (Corcoran et al, 2005).…”

Section: Lateral Amygdala In the Acquisition Of Fear Extinctionmentioning

confidence: 99%

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

Sotres-Bayón

Bush

LeDoux

2007

Neuropsychopharmacol

256

207

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N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity underlying learning in a variety of brain systems. Fear extinction, which involves learning to suppress the expression of previously learned fear, appears to require NMDAR activation in the amygdala. However, it is unclear whether amygdala NMDARs are required for the acquisition of extinction learning, and it is unknown whether NR2B-containing NMDARs are required in fear extinction. Here, we assessed the effects of selective NR2B blockade with ifenprodil on fear extinction learning, and found that both systemic and intra-amygdala ifenprodil treatment, given before extinction training, impaired the initial acquisition, and subsequent retrieval of fear extinction. These results confirm previous evidence showing that NMDARs in the amygdala are involved in fear extinction, and additionally show that NR2B-containing NMDARs are required. Contrary to the conclusion of previous studies, our findings demonstrate NMDARs are required for the initial acquisition, rather than only the retention, of fear extinction learning. Thus, our results support a previously not known role for NMDA-dependent plasticity in the lateral amygdala during the acquisition of fear extinction.

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Extinction of emotional learning: Contribution of medial prefrontal cortex

Cited by 820 publications

References 23 publications

Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory

Prefrontocortical Dopamine Loss in Rats Delays Long-Term Extinction of Contextual Conditioned Fear, and Reduces Social Interaction Without Affecting Short-Term Social Interaction Memory

Mechanisms of fear extinction

Acquisition of Fear Extinction Requires Activation of NR2B-Containing NMDA Receptors in the Lateral Amygdala

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