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In-Depth Information
internal milieu, and uses this information, together with a set of learnt “rules” (Wise et al.
1996), to guide appropriate behaviour. The afferent and efferent connections of the PFC,
together with intrinsic connectivity, endow it with this range of functions. For example, the
PFC is involved in integrating highly processed sensory information received from afferents
arising from association cortical regions in the temporal and parietal lobes, and in mnemonic
and emotional processing, due to its connectivity with limbic structures (Groenewegen and
Uylings 2000). Reciprocal connections with the hypothalamus and brainstem afford the PFC
with visceral functions.
One aspect of executive function is working memory, the ability to maintain information
“in mind” for a short period of time in the presence of distracting stimuli (Goldman-Rakic
1995). The cellular basis for working memory is a persistent firing of networks of PFC
neurons with shared stimulus properties (Goldman-Rakic 1995). While neurons in other brain
regions also show repetitive firing during working memory, PFC neurons are unique in their
ability to maintain firing in the presence of distractions (Miller and Cohen 2001). At present
the persistent firing underlying working memory is thought to be mediated by a combination
of reverberant synaptic activity in networks of neurons, and activation of intrinsic
conductances in pyramidal neurons, such as plateau potentials (Wang 2001; Milojkovic et al.
2005; Durstewitz and Seamans 2006; Wang et al. 2006). Computational models suggest the
requirement for both reverberating activity within the PFC and intrinsic bistability (“up and
down” states; Marder et al. 1996; Wang 2001). In primates, executive functions are
performed by the dorsolateral region of the PFC. In rodents, this function is performed by the
medial prefrontal cortex (mPFC), which includes the prelimbic and infralimbic regions
(Heidbreder and Groenewegen 2003). The prelimbic region is primarily associated with
working memory tasks (Zahrt et al. 1997; Birrell and Brown 2000), while the infralimbic
region is primarily involved in regulation of emotions (see below; Quirk and Mueller 2008).
Despite some controversy in the past, it is now widely accepted that the rodent provides a
viable model for studying PFC function. The early criterion for classification of the mPFC
was based solely on connections with the mediodorsal thalamic nucleus, which led some to
doubt the presence of a functional mPFC in the rodent (Preuss and Kaas 1999). However
more recent analyses of the structure, based on neurochemical, functional and developmental
studies, have yielded convincing data showing that the mPFC in the rodent is the anatomical
correlate of the dorsolateral PFC in the primate (Uylings et al. 2003; Povysheva et al. 2006).
While early studies on the mPFC focused on its role in short-term forms of memory such
as working memory, more recent work has established a role for the mPFC in long-term
memory, such as the laying down of “rules” to shape behavioural responses and consolidation
of memories. The underlying mechanisms for these forms of long-term memory are thought
to be synaptic plasticity. This chapter will provide an overview of the current literature on
synaptic plasticity in the mPFC, primarily at excitatory synapses in the rodent mPFC.
2.
S
YNAPTIC
C
IRCUITRY IN THE
PFC
As with other neocortical regions, the mPFC is a laminated structure consisting of layers
1-6, with the majority of excitatory pyramidal neurons located in layer 2/3 and layer 5. In rats
the mPFC lacks a layer 4. Three main types of pyramidal neuron have been identified in the
