Biology Reference
In-Depth Information
stimulus (Brozoski et al. 1979; Simon et al. 1980; Robbins and Everitt 1996; Schultz 2002).
The dopamine signal in the mPFC is highly tuned to signal the reward value of an event and
its precise coincident release into the mPFC may signal such an event by evoking plasticity of
the ongoing glutamatergic activity (Schultz 2002).
There are two broad classes of dopamine receptor, classified according to their genetic
sequence and pharmacology: D1-type, comprising D1 and D5 receptors, and D2-type,
comprising D2, D3 and D4 receptors (Civelli et al. 1993). The predominant type of dopamine
receptor in the mPFC is D1-type receptors, which outnumber D2-type receptors several fold
(Smiley et al. 1994). D1 receptors are expressed mainly on pyramidal neurons in layer 5
(Gaspar et al. 1995) where they are located on the spines and dendrites of neurons (Smiley et
al. 1994; Bergson et al. 1995), and presynaptically on afferent terminals where they depress
transmitter release (Gao et al. 2001; Seamans et al. 2001; Paspalas and Goldman-Rakic 2005).
Dopaminergic afferents to the mPFC arise in the VTA (Thierry et al. 1973), where they
synapse onto dendritic spines and shafts of layer 5 and 6 neurons (Van Eden et al. 1987;
Sesack et al. 1995). Some dopaminergic terminals form synaptic “triads”, where a
dopaminergic terminal targets both a postsynaptic dendritic spine and an excitatory terminal
of another afferent (Van Eden et al. 1987; Goldman-Rakic et al. 1989; Verney et al. 1990;
Sesack et al. 1995), although the main form of transmission is thought to be via volume
transmission (Garris and Wightman 1994). In addition to the phasic release of dopamine from
VTA afferents, for example during expectation of reward (Schultz 2002), slow tonic activity
maintains ambient levels of dopamine in the PFC (Bassareo and Di Chiara 1997; Takahata
and Moghaddam 2000). This may regulate the sensitivity of PFC neurons to forthcoming
inputs (Williams and Goldman-Rakic 1995).
The effects of dopamine on basal synaptic transmission in the PFC have been extensively
studied in vitro, yielding somewhat conflicting data (see Seamans and Yang 2004). However
the general consensus is that dopamine depresses single EPSPs evoked by local stimulation in
vitro (Gao et al. 2001; Seamans et al. 2001) or hippocampal stimulation in vivo (Gurden et al.
1999), but enhances NMDA receptor-mediated responses evoked with repetitive stimulation
(Seamans et al. 2001; Seamans and Yang 2004). Stimulation of the VTA in vivo evokes a
transition of layer 5 pyramidal neurons into an up state, while at the same time decreasing the
number of evoked action potentials (Lewis and O'Donnell 2000).
The effects of dopamine on synaptic plasticity in the mPFC are discussed above. In
summary, however, dopamine can facilitate either LTD or LTP. LTD is facilitated by
dopamine at layer 2/3 inputs to layer 5 pyramidal neurons, through a mechanism involving
mGluRs and activation of MAP kinase (Otani et al. 1998; Otani et al. 1999). Alternatively,
prior exposure to dopamine can “prime” synapses to evoke LTP (Blond et al. 2002; Matsuda
et al. 2006). At hippocampal inputs, the effect of dopamine is a facilitation of LTP. For
example, infusion of dopamine into the mPFC enhances LTP following tetanic stimulation of
the hippocampus (Jay et al. 1996). Furthermore, tetanic stimulation of the VTA at 50 Hz for 2
seconds, which releases dopamine into the mPFC (Garris et al. 1993) prior to stimulation of
the hippocampus, leads to a persistently enhanced LTP at hippocampal-mPFC synapses
(Gurden et al. 1999). Moreover disruption of the mesocortical dopaminergic projection from
the VTA to the PFC impairs LTP induction at hippocampal-mPFC synapses (Gurden et al.
1999; Gurden et al. 2000). This effect is mediated by D1 receptors, demonstrated by the fact
that infusion of a D1 agonist into the PFC prior to tetanic stimulation of the hippocampus
enhances LTP, while infusion of a D1 antagonist into the PFC blocks LTP (Gurden et al.
