Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission

Abstract

SUMMARY The paraventricular nucleus of the thalamus (PVT) is thought to regulate behavioral responses under emotionally arousing conditions. Reward-associated cues activate PVT neurons, however, the specific PVT efferents regulating reward-seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT activity under two emotionally distinct conditions: 1) when reward was available during the cue as expected, or 2) when reward was unexpectedly omitted during the cue. Pharmacological inactivation of the anterior PVT (aPVT), but not the posterior PVT, increased sucrose-seeking only when reward was omitted. Consistent with this, photoactivation of aPVT neurons abolished sucrose-seeking, and the firing of aPVT neurons differentiated reward availability. Photoinhibition of aPVT projections to the nucleus accumbens or to the amygdala increased or decreased, respectively, sucrose-seeking only when reward was omitted. Our findings suggest that PVT bidirectionally modulates sucrose-seeking under the negative (frustrative) conditions of reward omission.

Optogenetic activation of amygdala projections to nucleus accumbens can arrest conditioned and unconditioned alcohol consummatory behavior

“…It is not clear whether we would have seen similar effects of stimulating other excitatory glutamatergic inputs into the AcbSh although recent studies support a role for multiple inputs, including the prefrontal cortex and the thalamus, in reward seeking and consumption (Britt et al, 2012; Do-Monte et al, 2017; Prado et al, 2016; Selleck and Baldo, 2017; Stuber et al, 2011). For example, Britt et al found that mice will respond for activation of prefrontal, BLA, or hippocampual accumbal inputs (Britt et al, 2012).…”

“…The prefrontal cortex has been suggested to be critical for behavior selection and for switching between appetitive and consummatory behavior (c.f.,(Selleck and Baldo, 2017). Additionally, activation of inputs from the paraventricular nucleus of the thalamus during instrumental nosepoking for sucrose decreases nosepoke responding, yet did not reduce ad libitum sucrose consumption (Do-Monte et al, 2017). Notably, our study used a stimulation train of five seconds, while others (c.f., Britt et al, 2012; Do-Monte et al, 2017) utilize stimulation trains ranging from one to fifteen seconds, which may drive AcbSh units more powerfully than typically observed; while there is utility in probing potential functionality using current optogenetics approaches, studies that attempt to mimic natural activity patterns using brief and low intensity stimulation are a future goal.…”

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

“…Additionally, the PVT-NAc pathway is involved in the acquisition of cocaine self-administration (Neumann et al 2016), as well as mediating symptoms during drug withdrawal (Zhu et al 2016). Recently, however, it was shown that pharmacological inactivation of the anterior, but not the posterior, PVT increases sucrose-seeking behavior upon reward omission, and that this behavior is specifically mediated by aPVT projections to the NAc shell (Do-Monte et al 2017). In contrast, differences in food-cue-induced neuronal activity between STs and GTs seems to be restricted to cells projecting from the posterior PVT (pPVT) to the “shore” (area bordering the core/shell) of the nucleus accumbens (Haight et al, 2017).…”

“…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).…”