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receptors for induction but not maintenance since induction can be blocked by infusion of
AP5 into the prelimbic PFC (Laroche et al. 1990; Jay et al. 1995; 1996).
Dopaminergic input from the VTA is also required for LTP at hippocampal-mPFC
synapses. Jay and colleagues showed that lesioning the VTA reduced LTP, while stimulating
the VTA enhanced LTP evoked with a moderate induction protocol (Gurden et al. 1999).
Consistent with this, infusion of a D1 agonist enhanced LTP, while infusion of a D1
antagonist blocked LTP at these inputs (Gurden et al. 2000; Matsumoto et al. 2008). The
actions of DA acting on D1 receptors is presumably via activation of PKA, since LTP at these
inputs was blocked by the PKA inhibitor Rp-cAMPs (Gurden et al. 2000). A recent study
showed that D1 receptors are also required for short-term plasticity at hippocampal-PFC
synapses in vivo (Goto and Grace 2007).
LTD has also been evoked at hippocampal-PFC synapses, by low frequency tetanic
stimulation (trains of 5 stimuli at 250 Hz, repeated 900 times at 1 Hz; Takita et al. 1999; Izaki
et al. 2001). This was reversible upon high frequency stimulation (50 pulses at 250 Hz,
repeated 12 times; Takita et al. 1999). In contrast to the traditional induction protocol that
induces LTD in other brain regions (single stimuli at 1 Hz repeated 900 times for 15 minutes;
Dudek and Bear 1992; Kirkwood et al. 1993; Dudek and Friedlander 1996; Manabe 1997)),
this protocol failed to induce LTD in the mPFC but instead led to depotentiation of evoked
LTP in vivo (Burette et al. 1997).
Neurons in the hippocampus oscillate in the theta (4-10 Hz) range during exploratory
behaviour and REM sleep (Green and Arduini 1954; Vanderwolf 1969; Buzsaki 2002), both
of which are thought to be involved in memory formation. Furthermore the mPFC is
entrained to theta rhythms in the hippocampus in freely behaving rats (Siapas et al. 2005) and
during spatial working memory tasks (Jones and Wilson 2005). Despite this, however, only
one study has examined plasticity at hippocampal-PFC synapses using theta burst stimulation.
In this study only STP was evoked with moderate strength theta burst stimulation (Goto and
Grace 2007). Neuronal firing rates have also been measured at 1 Hz in CA1 pyramidal
neurons in the awake rat, and ripple activity has been observed at approximately 250 Hz,
suggesting that these frequencies, which have been used for inducing longer-term plasticity,
are also behaviourally relevant (Suzuki and Smith 1988; Ylinen et al. 1995). The implications
for plasticity at hippocampal-mPFC synapses are discussed below.
(iii) PFC-amygdala interactions
The amygdala is involved in generating emotions and emotional memories, in particular
fear-related memories, in response to sensory inputs (Sah et al. 2003). The mPFC and the
amygdala have reciprocal connections (Cassell and Wright 1986; Cassell et al. 1989;
McDonald 1991; 1996; McDonald et al. 1996) and this circuit has been shown to be crucial
for integrating emotionally salient stimuli and regulating emotional memories (Milad and
Quirk 2002; Ochsner and Gross 2005; Laviolette and Grace 2006). Medial PFC neurons can
inhibit (Rosenkranz and Grace 1999; 2001; 2002) or excite (Likhtik et al. 2005) amygdala
neurons, and project directly to inhibitory intercalated cells in the amygdala (McDonald et al.
1996). Conversely, amygdala neurons excite parvalbumin-containing interneurons in the
mPFC (Gabbott et al. 2006), but stimulation of the basolateral amygdala evokes both
inhibitory and excitatory responses in the mPFC (Perez-Jaranay and Vives 1991). NMDA
