Article

Morgan MA, Schulkin J, LeDoux JE. Ventral medial prefrontal cortex and emotional perseveration: the memory for prior extinction training. Behav Brain Res 146: 121-130

Georgetown University, Washington, Washington, D.C., United States
Behavioural Brain Research (Impact Factor: 3.03). 12/2003; 146(1-2):121-30. DOI: 10.1016/j.bbr.2003.09.021
Source: PubMed

ABSTRACT

Several years ago, we found that lesions of ventral medial prefrontal cortex (mPFCv) disrupted performance during the extinction component of a classical fear conditioning task without affecting acquisition performance. We called this emotional perseveration, hypothesizing that mPFCv may normally act to inhibit fear responses to a conditioned stimulus (CS) when the CS no longer signals danger. Subsequent studies have supported this hypothesis, showing that mPFCv is crucial for the memory of prior extinction training. The present study examined the effects of mPFCv lesions made after training. Such lesions resulted in reduced freezing to contextual stimuli and normal responding to the CS presented alone during a retention test. Rats were then subjected to extinction trials (CS without US) over multiple days. In contrast to pre-training lesions, post-training lesions had little effect on extinction rate. All rats were given additional training. Lesioned rats expressed greater fear reactions than controls, indicating that prior extinction was less effective in them. Lesioned rats also showed resistance to extinction during reextinction trials, confirming our earlier finding that lesions made before training weaken the effectiveness of extinction trials. These results suggest three conclusions. First, an intact mPFCv during acquisition may protect the animal from prolonged responding during extinction trials following brain insult. Second, changes in mPFCv may predispose subjects toward enhanced fear reactions that are difficult to extinguish when reexposed to fearful stimuli, due to a diminished capacity to benefit from the fear-reducing impact of prior extinction experience. Third, contextual cues processed by mPFCv may influence extinction performance.

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Available from: Jay Schulkin, Aug 18, 2014
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    • "H.Kim & Richardson, 2008;Laurent, Marchand, & Westbrook, 2008). On the other side, the ventral medial prefrontal cortex has been shown to play an important role in the effectiveness of extinction and reextinction processes (Morgan, Schulkin, & LeDoux, 2003). All these extinction-related findings support the idea that a previous learning experience— either the acquisition or the inhibition of fear— can alter the molecular mechanisms that trigger, respectively, the acquisition or the extinction of subsequent memories not only in the hippocampus but also in the amygdala. "
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    • "The vmPFC activates GABAergic intercalated cells in the amygdala which in turn inhibit the central nucleus of the amygdala (Quirk et al., 2006; Sotres-Bayon et al., 2007). Evidence for this model has been provided by lesion studies (Morgan and LeDoux, 1993; Quirk et al., 2000; Morgan et al., 2003; Lebron et al., 2004). For example Morgan and LeDoux (1993) showed that rats with lesions of the medial PFC were resistant to extinction learning in a delay fear conditioning paradigm. "
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    • "Studies in animals (Maren & Quirk, 2004; Pare et al., 2004) and humans (Phelps & LeDoux, 2005) indicate that interactions between the medial prefrontal cortex (mPFC) and the amygdala are critically involved in extinction learning (Morgan et al., 1993; LeDoux, 2000; Quirk et al., 2003; Rosenkranz et al., 2003). Specifically, recent studies have established a role for the infralimbic prefrontal cortex (IL) in consolidation of fear extinction (Milad & Quirk, 2002; Morgan et al., 2003; Sierra-Mercado et al., 2006). Previous studies also implicate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathways in consolidation of auditory and contextual fear conditioning (Schafe et al., 2000; Trifilieff et al., 2006), as well as extinction of conditioned fear in the mPFC, BLA, "
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