Biology Reference
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NMDA receptors and D1 and D2 receptors, but instead can be blocked by the cannabinoid
antagonist AM251 or by the mGluR5 antagonist MPEP (Lafourcade et al. 2007).
Actions of endocannabinoids in the mPFC also play a role in the expression of olfactory
fear conditioning. Infusion of a CB1 receptor agonist into the mPFC potentiates the fear
response in this paradigm, while infusion of a CB1 antagonist blocks the fear response
(Laviolette and Grace 2006). This correlates with single unit recordings in vivo, which
showed an increase in burst firing in mPFC neurons that receive inputs from the basolateral
amygdala during presentations of a conditioned stimulus. Burst firing was potentiated by
microinfusions of a CB1 receptor agonist into the mPFC but blocked by a CB1 receptor
antagonist (Laviolette and Grace 2006), showing that cannabinoid receptor activation in the
mPFC is necessary for this form of emotional learning. Since cannabinoids mediate LTD of
excitatory inputs in the mPFC in vitro (Lafourcade et al. 2007), these data present an apparent
disparity between in vitro and in vivo studies. Thus the cellular basis of the actions of
cannabinoids in olfactory fear conditioning remains to be elucidated, however this effect may
be specific to afferents from the basolateral amygdala to the mPFC.
6.
R
OLES
O
F
P
LASTICITY IN THE
PFC
There are a number of lines of evidence pointing to a role of the mPFC in long-term
memory. In humans, neuropsychological and neuroimaging studies have provided this
evidence (Janowsky et al. 1989; Shimamura 1995; Buckner and Koutstaal 1998), while
imaging and electrophysiological studies have shown a role for the mPFC in humans and
primates in long-term recognition memory (Parkin et al. 1996; Schacter et al. 1996; Tulving
et al. 1996; Kopelman and Stanhope 1998; Cabeza and Nyberg 2000; Lee et al. 2000a;
Cadoret et al. 2001; Dobbins et al. 2002; Kikyo et al. 2002; Konishi et al. 2002; Petrides et al.
2002; Rugg et al. 2002; Xiang and Brown 2004). Disruption of PFC function with
transcranial magnetic stimulation impairs formation of a visual recognition memory during
episodic memory learning tasks, providing direct evidence a role for the PFC in the storage of
long-term memories (Rossi et al. 2001; Rossi et al. 2006). Furthermore patients with damage
to the PFC show similar impairments in remembering contextual details to patients with
temporal lobe damage (Shimamura et al. 1990; Simons et al. 2002).
Initial evidence for the role of the PFC in long-term memory formation in animals derives
from the observation that only trained animals show persistent firing during the delay period
of a spatial working memory task (see below; Fuster 1973). This suggests that learning the
working memory task involves plastic changes. Furthermore during operant conditioning rats
exhibit either long-term decreases or increases in neuronal activity in the mPFC (Mulder et al.
2000). This requires simultaneous activation of D1 receptors, NMDA receptors and PKA in
the mPFC (Baldwin et al. 2002), consistent with in vitro and in vivo studies of LTP in the
mPFC (Hirsch and Crepel 1991; Gurden et al. 2000). In addition, long-term changes in the
activity of mPFC neurons are involved in extinction of conditioned fear responses (see
above). Specific roles of long-term memory in the mPFC are discussed below.
