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receptor-dependent LTP can be evoked in the prelimbic mPFC following theta burst
stimulation (10 trains of ten stimuli at 100 Hz, repeated 3 times) of the rat basolateral
amygdala in vivo (Maroun and Richter-Levin 2003).
Emotional memory formation has been widely studied using a form of Pavlovian
associative learning, fear conditioning. This involves pairing an unconditioned stimulus,
which evokes fear, with a neutral conditioned stimulus, such that subsequent exposure to the
conditioned stimulus elicits a fear response (Pavlov 1927). Plasticity underlying this effect is
known to occur within the amygdala (LeDoux 2000), since lesions or inactivation of the
amygdala before conditioning prevent the animal from learning fear associations (Iwata et al.
1986; Goosens and Maren 2003), while lesions of the amygdala following conditioning
prevent the expression of the fear response (Anglada-Figueroa and Quirk 2005). While initial
experiments showed that lesioning the mPFC had no effect on the acquisition or expression of
conditioned fear (Rosen et al. 1992; Quirk et al. 2000), recent evidence suggests that the
mPFC is involved in the expression of fear conditioning. Inactivation of the prelimbic mPFC
suppresses fear responses following conditioning (Blum et al. 2006; Corcoran and Quirk
2007), and the prelimbic mPFC shows increased firing following conditioning (Baeg et al.
2001; Gilmartin and McEchron 2005; Laviolette et al. 2005). Furthermore microstimulation
of the prelimbic mPFC enhances conditioned fear responses (Vidal-Gonzalez et al. 2006).
Thus the results of the initial lesioning experiments may have been confounded by
compensatory measures occurring following lesioning, and do not discount the possibility
that the intact mPFC contributes to expression of fear conditioning (Quirk and Mueller 2008).
In view of the excitatory projections from the mPFC to the basolateral amygdala (McDonald
et al. 1996), and the finding that firing in the prelimbic mPFC precedes that in the amygdala,
this suggests that the prelimbic mPFC may drive the basolateral amygdala during expression
of fear responses (Vertes 2004; Likhtik et al. 2005).
The mPFC also plays an important role in extinction of fear conditioning. Extinction to a
conditioned stimulus occurs when exposure to the conditioned stimulus is repeated in the
absence of the unconditioned stimulus, thereby eliminating the fear memory (Pavlov 1927;
Myers and Davis 2002). Extinction involves new learning as opposed to “unlearning” of the
fear memory (Pavlov 1927; Bouton et al. 2006; Myers and Davis 2007). There are three
phases of extinction: acquisition, consolidation, and retrieval. Acquisition is the initial
learning, consolidation follows for several hours afterwards and involves cellular and
molecular mechanisms of memory storage, and retrieval occurs during a subsequent testing
(Quirk and Mueller 2008).
The mPFC is not required for acquisition of extinction, since mPFC lesions have no
effect on the acquisition of extinction in rodents (Gewirtz et al. 1997; Quirk et al. 2000;
Vouimba et al. 2000), and no association has been found between extinction acquisition and
plasticity in the mPFC (Herry and Garcia 2002). However one study did show an acceleration
of extinction acquisition when tetanic stimulation of the infralimbic cortex was combined
with presentations of the conditioned stimulus alone (Milad and Quirk 2002). The amygdala
is the primary area that has been attributed with the acquisition of extinction, demonstrated
through lesioning studies and infusion of compounds that inhibit synaptic plasticity into the
basolateral region of the amygdala (for review see Quirk and Mueller 2008).
A number of studies have implicated the infralimbic mPFC in the consolidation of
extinction (Quirk et al. 2000; Weible et al. 2000; Fernandez Espejo 2003; Morgan et al. 2003;
Lebron et al. 2004). For example, lesioning the infralimbic mPFC prevents retrieval of the
