Reconsolidation and extinction of conditioned fear: inhibition and potentiation

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Reconsolidation and extinction of conditioned fear : inhibition and potentiation. / Lee, Jonathan L C; Milton, Amy L; Everitt, Barry J.

In: The Journal of Neuroscience, Vol. 26, No. 39, 2006, p. 10051-6.

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Lee, Jonathan L C ; Milton, Amy L ; Everitt, Barry J. / Reconsolidation and extinction of conditioned fear : inhibition and potentiation. In: The Journal of Neuroscience. 2006 ; Vol. 26, No. 39. pp. 10051-6.

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@article{a5acf66f7bef45eba73e924f6c0975de,
title = "Reconsolidation and extinction of conditioned fear: inhibition and potentiation",
abstract = "NMDA receptors are important for the acquisition, reconsolidation, and extinction of memories. NMDA receptor antagonists impair these memory processes, whereas the partial agonist D-cycloserine (DCS) potentiates both learning and extinction. Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to investigate the effects of enhancing and blocking NMDA receptor-mediated glutamatergic transmission on the reconsolidation and extinction of a conditioned fear memory. Either long extinction training or short memory reactivation sessions were used to preferentially engage extinction and reconsolidation processes, respectively. MK-801 blocked extinction to maintain high levels of conditioned freezing, and DCS potentiated extinction to reduce freezing, when they were administered before a long extinction training session. However, the opposite behavioral outcome was observed when the brief memory reactivation session was used: MK-801 administration impaired, whereas DCS increased, freezing, likely reflecting impairment and enhancement of reconsolidation, respectively. Finally, by using localized intracerebral infusions, we showed that the basolateral amygdala is a primary locus of action of systemically administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the extinction and the reconsolidation of fear conditioning, depending on the length of the extinction/memory reactivation session. Therefore, memory reconsolidation can be both disrupted and enhanced, and extinction can be both potentiated and impaired, either to reduce or increase conditioned fear. These results have important implications for the use of reconsolidation blockade and potentiation of extinction as treatment strategies for maladaptive memory disorders.",
author = "Lee, {Jonathan L C} and Milton, {Amy L} and Everitt, {Barry J}",
year = "2006",
doi = "10.1523/JNEUROSCI.2466-06.2006",
language = "English",
volume = "26",
pages = "10051--6",
journal = "The Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "39",

}

RIS

TY - JOUR

T1 - Reconsolidation and extinction of conditioned fear

T2 - inhibition and potentiation

AU - Lee, Jonathan L C

AU - Milton, Amy L

AU - Everitt, Barry J

PY - 2006

Y1 - 2006

N2 - NMDA receptors are important for the acquisition, reconsolidation, and extinction of memories. NMDA receptor antagonists impair these memory processes, whereas the partial agonist D-cycloserine (DCS) potentiates both learning and extinction. Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to investigate the effects of enhancing and blocking NMDA receptor-mediated glutamatergic transmission on the reconsolidation and extinction of a conditioned fear memory. Either long extinction training or short memory reactivation sessions were used to preferentially engage extinction and reconsolidation processes, respectively. MK-801 blocked extinction to maintain high levels of conditioned freezing, and DCS potentiated extinction to reduce freezing, when they were administered before a long extinction training session. However, the opposite behavioral outcome was observed when the brief memory reactivation session was used: MK-801 administration impaired, whereas DCS increased, freezing, likely reflecting impairment and enhancement of reconsolidation, respectively. Finally, by using localized intracerebral infusions, we showed that the basolateral amygdala is a primary locus of action of systemically administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the extinction and the reconsolidation of fear conditioning, depending on the length of the extinction/memory reactivation session. Therefore, memory reconsolidation can be both disrupted and enhanced, and extinction can be both potentiated and impaired, either to reduce or increase conditioned fear. These results have important implications for the use of reconsolidation blockade and potentiation of extinction as treatment strategies for maladaptive memory disorders.

AB - NMDA receptors are important for the acquisition, reconsolidation, and extinction of memories. NMDA receptor antagonists impair these memory processes, whereas the partial agonist D-cycloserine (DCS) potentiates both learning and extinction. Here, we used DCS and the noncompetitive NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-SH-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) to investigate the effects of enhancing and blocking NMDA receptor-mediated glutamatergic transmission on the reconsolidation and extinction of a conditioned fear memory. Either long extinction training or short memory reactivation sessions were used to preferentially engage extinction and reconsolidation processes, respectively. MK-801 blocked extinction to maintain high levels of conditioned freezing, and DCS potentiated extinction to reduce freezing, when they were administered before a long extinction training session. However, the opposite behavioral outcome was observed when the brief memory reactivation session was used: MK-801 administration impaired, whereas DCS increased, freezing, likely reflecting impairment and enhancement of reconsolidation, respectively. Finally, by using localized intracerebral infusions, we showed that the basolateral amygdala is a primary locus of action of systemically administered DCS. Thus, intrabasolateral amygdala DCS potentiated both the extinction and the reconsolidation of fear conditioning, depending on the length of the extinction/memory reactivation session. Therefore, memory reconsolidation can be both disrupted and enhanced, and extinction can be both potentiated and impaired, either to reduce or increase conditioned fear. These results have important implications for the use of reconsolidation blockade and potentiation of extinction as treatment strategies for maladaptive memory disorders.

U2 - 10.1523/JNEUROSCI.2466-06.2006

DO - 10.1523/JNEUROSCI.2466-06.2006

M3 - Article

C2 - 17005868

VL - 26

SP - 10051

EP - 10056

JO - The Journal of Neuroscience

JF - The Journal of Neuroscience

SN - 0270-6474

IS - 39

ER -