4.4. Medial prefrontal cortex (mPFC)
The mPFC is a key component of the mesolimbic reward system. It is involved in the evaluation of the salience and motivational significance of reward-paired cues, and in selection and initiation of motivated actions (Moorman and Aston-Jones 2015; Moorman et al. 2015). The mPFC is often divided into prelimbic and infralimbic regions, which have very different projection patterns and can play different roles in reward-driven behavior. Although both are connected with several areas that are involved in motivation and emotion, such as the VTA, hippocampus, and amygdala, and PVT (Li and Kirouac 2012; Vertes 2004), there are especially prominent projections to the NAcc. The prelimbic cortex projects primarily to the NAcc core, and the infralimbic cortex projects primarily to the NAcc shell (Vertes 2004). These pathways have been shown to have opposite effects on a range of motivated behaviors, such as cocaine self-administration (LaLumiere et al. 2010; Peters et al. 2008; Peters et al. 2009), sucrose reinforcement (Peters and De Vries 2013), and conditioned fear (Maren and Quirk 2004; Peters et al. 2009). The prelimbic cortex is important for the acquisition of excitatory conditioning (Meyer and Bucci 2014), and often acts as a “go” signal that instigates reward seeking; whereas the infralimbic cortex is important for the expression of well-learned inhibitory behavior, acting as a “stop” signal that suppresses previously learned conditioned responses (LaLumiere et al. 2010; Peters et al. 2009; Peters and De Vries 2013). However, other studies suggest that the function of the mPFC is more complex than this simple dichotomy (Moorman et al. 2015); for example, the prelimbic cortex has also been shown to inhibit dominant responses in favor of more adaptive, goal-driven behavior (Meyer and Bucci 2014).
In addition to its role in the expression of reward-seeking, the mPFC is important for the consolidation of reward-related memories during sleep. For example, the ability of sleep deprivation to enhance sucrose seeking and consumption is associated with a selective weakening of the glutamatergic pathway from the mPFC to the NAcc (Liu et al. 2016). The mPFC also has strong functional connections with the hippocampus. It receives direct projections from the ventral hippocampus CA1 (Adhikari et al. 2010; Hoover and Vertes 2007), and studies that have recorded from both the mPFC and hippocampus have found correlations between spike times in the two regions, as well as coherent theta rhythms (Adhikari et al. 2010; Benchenane et al. 2010; Colgin 2011). Furthermore, the mPFC and hippocampus reactivate together during slow-wave sleep, with synchronous bursts of activity occurring in both structures during sharp-wave ripples in the hippocampus (Colgin 2011; Wierzynski et al. 2009).
The mPFC also mediates aspects of executive function that may be particularly relevant to STs and GTs, such as impulsivity and attentional control. It has been shown that STs have low levels of cholinergic activity in the mPFC relative to GTs, and that this causes poor attentional control in STs compared to GTs (Paolone et al. 2013). At the same time, STs have greater dopamine responses to cues in the mPFC than GTs, which couple with low cholinergic activity, is thought to contribute to the reduced “top-down” control of behavior seen in STs relative to GTs (Pitchers et al. 2017). Furthermore, as mentioned above, projections from the prelimbic cortex to the PVT are thought to mediate behavioral control in GTs (Haight et al. 2017). Therefore, given that the mPFC plays such a prominent role in multiple reward-seeking paradigms, consolidation of reward memories during sleep, and individual differences in incentive salience attribution, we believe this this is an area where fundamental phenotypic differences in ST/GT neurocircuitry are very likely to be observed.