Biology Reference
In-Depth Information
cellular mechanisms is important for developing treatments for post-traumatic stress disorder
and anxiety disorders, since they are thought to result from the inability to extinguish fear
memories (see below).
5.
N
EUROMODULATION OF
S
YNAPTIC
P
LASTICITY IN THE
PFC
Removing catecholamines from the PFC is as detrimental to the functioning of the PFC
as removal of the PFC itself (Brozoski et al. 1979), pointing to the vital role that
neuromodulators serve in the functioning of this brain region. In addition, a large body of
evidence has shown that neuromodulators play an important role in regulating synaptic
plasticity. These are discussed below.
While all cortical regions receive inputs from monoaminergic and cholinergic systems,
leading to the release of dopamine, noradrenaline, 5-hydroxytryptamine (5-HT) and
acetylcholine, it is only the mPFC that sends projections back to these brainstem structures,
endowing the mPFC with control over the functioning of these neuromodulator systems
(Arnsten 1997; Everitt and Robbins 1997). Serotonergic neurons arise in the raphe nuclei
project to the mPFC (Azmitia and Segal 1978). Lesioning these inputs with 5,7-
dihydroxytryptamine (5,7-DHT) augments LTP of field EPSPs in the prelimbic mPFC,
evoked by high frequency stimulation of CA1 (50 trains at 250 Hz; Ohashi et al. 2003). This
suggests that 5-HT attenuates LTP at hippocampal-mPFC synapses, potentially via a
depression of NMDA receptor-mediated currents (Staubli and Otaky 1994; Edagawa et al.
1999).
Afferents from the locus coeruleus densely innervate the mPFC, where they release
noradrenaline (Levitt and Moore 1978; Lindvall et al. 1978; Morrison et al. 1978; Aoki et al.
1998). Noradrenaline is important for extinction of fear memories, as it has been shown that
noradrenaline is released into the mPFC during fear extinction (Hugues et al. 2007), and
depletion of forebrain noradrenaline impairs extinction retrieval (Mason and Iversen 1977).
Furthermore activation of beta adrenoceptors in the mPFC is required for consolidation of
extinction (Mueller et al. 2008) and odour reward memories (see below; (Tronel et al. 2004)),
suggesting that activation of beta adrenoceptors may facilitate LTP. In contrast, recent
evidence suggests that activation of alpha adrenoceptors promotes LTD. Activation of both
1 and 2 adrenoceptors by noradrenaline evokes LTD, and this is mediated by activation of
NMDA receptors, PKC and extracellular signal-regulated kinase 1/2 (ERK1/2; Marzo et al.
2007).
(i) Dopamine
Dopamine levels in the mPFC are essential for normal functioning, for example in
working memory. Dopamine exhibits an inverted U-shaped dose response curve, whereby
levels of dopamine that are either too low or too high impair proper functioning
(Vijayraghavan et al. 2007). As well as being essential for working memory (Sawaguchi and
Goldman-Rakic 1991; 1994; Seamans et al. 1998; Floresco and Phillips 2001; Seamans and
Yang 2004), dopaminergic systems are also involved in predicting the reward value of a
