Prefrontal cortex output circuits guide reward seeking through divergent cue encoding

Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking

“…NAc is a known regulator of reward seeking (Creed et al, 2015; Lobo and Nestler, 2011) and risk evaluation (Zalocusky et al, 2016); a direct top-down glutamatergic projection from mPFC would be well positioned to mediate punishment-encoding responses and suppression of reward seeking, for example, through direct activation of D2R neurons or indirect inhibition of D1R neurons via local parvalbumin interneurons (Calipari et al, 2016; Kravitz et al, 2012; Qi et al, 2016) or direct stimulation of dynorphin neurons (Al-Hasani et al, 2015). While the role of glutamatergic inputs to the medial core of NAc in promoting reward seeking has been studied (Britt et al, 2012; Otis et al, 2017; Pascoli et al, 2014; Qi et al, 2016; Stuber et al, 2011), here, we demonstrate that glutamatergic inputs to lateral shell of NAc can encode and drive punishment or aversion responses. Furthermore, while previous work reported that cocaine-activated neurons in mPFC exhibit high levels of NPAS4 expression and project to medial shell of NAc (Ye et al, 2016), we here did not observe elevated expression of NPAS4 in mPFC neurons that project to lateral shell of NAc and drive aversion.…”

“…Previous studies have highlighted a role of mPFC in suppression of natural and drug-related reward seeking (Bossert et al, 2012; Ferenczi et al, 2016; Pfarr et al, 2015) and during conflicted reward-seeking tasks (Amemori and Graybiel, 2012; Friedman et al, 2015; St Onge et al, 2012; Peters and Büchel, 2009; St Onge and Floresco, 2010); however, opposing results obscure which specific region or projection of mPFC neurons may mediate these aversion-related behaviors. For example, some studies have found that the prelimbic (PL) subregion of mPFC promotes reward seeking (McFarland et al, 2004; McLaughlin and See, 2003; Otis et al, 2017), while others found inhibition of responding for reward (Chen et al, 2013a; Jonkman et al, 2009). Cellular-level and brainwide investigation of how circuits carry out this transformation of a complex choice into unitary action may thus require advances in the ability to manipulate and measure brain-spanning circuit activity patterns during behavior.…”

Transient inactivation of the paraventricular nucleus of the thalamus enhances cue-induced reinstatement in goal-trackers, but not sign-trackers

“…In the current study, however, we targeted a specific nucleus that had been identified as a key player in these Pavlovian learning processes (Flagel et al 2011a, Haight and Flagel 2014, Haight et al 2015, Yager et al 2015, Haight et al 2017), to determine whether the same nucleus acts to encode the incentive value of a cue that was previously paired with operant drug delivery. While it is known that the neural circuitry mediating Pavlovian conditioning can differ from that mediating instrumental behavior (Ostlund et al 2007, Yin et al 2008, Wassum et al 2011), the paraventricular nucleus of the thalamus appears to be involved in both (Hamlin et al 2009, James et al 2010, Browning et al 2014, Haight et al 2015, Matzeu et al 2015, Neumann et al 2016, Do-Monte et al 2017, Matzeu et al 2017, Otis et al 2017). The current findings support a role for this nucleus in the attribution of incentive value to reward cues and suggest that, in a subset of individuals, the PVT acts to suppress the learned incentive value of such cues.…”

“…The PVT is a midline thalamic structure that acts as an interface between cortical, limbic and motor circuits, relaying information regarding arousal and reward, among other functions, to the striatum (Kelley et al 2005). Thus, it is not surprising that this nucleus has been implicated in reward learning (Flagel et al 2011a, Haight et al 2015, Yager et al 2015, Do-Monte et al 2017, Haight et al 2017, Ong et al 2017, Otis et al 2017) as well as a number of other complex behaviors, including fear learning (Li et al 2014, Do-Monte et al 2015, Penzo et al 2015) and anxiety-related behaviors (Li et al 2010, Barson et al 2015). Work from our laboratory suggests that the PVT acts as a central node via the hypothalamic-thalamic-striatal axis to regulate the attribution of incentive salience to reward cues and the expression of the resultant behaviors (Haight et al 2017).…”

Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

“…Identified candidate top-down circuits arising from frontal cortices include direct inputs to posterior sensory cortices, thalamus, and claustrum (Miller and Buschman, 2013; Zhang et al, 2014; Mathur, 2014). Given that prefrontal cortex neurons can encode task performance differentially based on projection target (Otis et al, 2017), it is critical to determine which signals are being propagated to claustrum, for instance, and how these signals (Zhang et al, 2016). …”