Biology Reference
In-Depth Information
exposure to an enriched environment (Meredith et al. 2007), which has been shown to
enhance dendritic growth and spine numbers in the mPFC.
(a) Schizophrenia
Disruption of cognitive function, including working memory, is a key feature of
schizophrenia (Carter et al. 1998; Manoach 2003; Elvevag and Goldberg 2000). Bilateral
hypofunction of the PFC has been shown to occur in schizophrenia patients, leading to
profound deficits in working memory and attention (Weinberger et al. 1986; Arnsten 2007).
In patients with schizophrenia, synaptic connectivity in the PFC is altered, particularly in
layer 3 (Lewis and Anderson 1995; Lewis and Gonzalez-Burgos 2008), and layer 3 pyramidal
neurons show reduced soma size and have reduced inhibitory inputs (Lewis and Gonzalez-
Burgos 2000). Aberrations in the dopamine system in the mPFC are considered a major
feature in the pathology of schizophrenia (Grace 1991; Carlsson et al. 2001). Moreover
functional connectivity between the hippocampus and the mPFC is likely to be impaired
given that a common symptom of schizophrenia is the inability to integrate contextual
information (Bazin et al. 2000; Harrow et al. 2000; Stratta et al. 2000). Consistent with this,
neonatal lesions of the ventral hippocampus, which sends a heavy projection to the mPFC,
serve as an animal model for schizophrenia (Lipska and Weinberger 2002). Finally,
clozapine, the atypical antipsychotic drug which at present is the most effect treatment for
schizophrenia, has been shown to facilitate synaptic plasticity at hippocampal inputs to the
mPFC (Dupin et al. 2006; Matsumoto et al. 2008). Together, these findings suggest that
aberrations in synaptic plasticity in the mPFC may contribute to the pathology of
schizophrenia. Future studies examining synaptic plasticity in the mPFC in animal models of
schizophrenia will help to elucidate the cellular basis of such aberrations.
(b) Anxiety disorders, stress and post-traumatic stress disorder
Stress has a deleterious effect on cognitive function, and impairs working memory
(McEwen and Sapolsky 1995). These deficits can be overcome by modulating DA levels in
the mPFC (Murphy et al. 1996a; Murphy et al. 1996b). Stress can either precipitate or
exacerbate other neurological disorders, such as depression, schizophrenia and Parkinson's
disease (Schwab and Zieper 1965). The mPFC plays a key role in the neurocircuitry
underlying responses to stress. For example it has been shown to modulate neuroendocrine
responses during stress (Meaney and Aitken 1985; McEwen et al. 1986), it is selectively
activated by both psychological and social stressors (Thierry et al. 1976), and acute stress
induces higher glutamate release into the mPFC. Glucocorticoids released during chronic
stress can cause atrophy of pyramidal cell apical dendrites and dendritic spines in layer 2/3 of
the mPFC (Wellman 2001; Radley et al. 2004; Brown et al. 2005; Cerqueira et al. 2007b) and
stress can impair spatial memory tasks and behavioural flexibility (Mizoguchi et al. 2000;
Cerqueira et al. 2007b). Thus submitting rats to acute stress by placing them on an elevated
platform for 30 minutes impairs LTP at hippocampal-PFC synapses, when evoked in vivo
within 180 minutes of the acute stress treatment. This effect can be reversed by antidepressant
treatment (Rocher et al. 2004). Chronic stress also impairs LTP at hippocampal-prelimbic
mPFC inputs (evoked by 10 trains of stimuli at 250 Hz; Goto and Grace 2006; Cerqueira et
al. 2007a). Conversely, stress evoked for only 10 minutes (by exposure to cold), facilitates
LTP at these inputs (evoked by 10 trains of stimuli at 250 Hz; Goto and Grace 2006).
