Orexin in the Posterior Paraventricular Thalamus Mediates Hunger-Related Signals in the Nucleus Accumbens Core

Animals use exteroceptive stimuli that have acquired, through learning, the ability to predict available resources allowing them to engage in adaptive behaviors. Meanwhile, peripheral signals related to internal state (e.g., hunger) provide information about current needs, modulating the ability of exteroceptive stimuli to drive food-seeking behavior [1, 2]. The nucleus accumbens core (NAcC) is essential for encoding the value of reward-predictive cues and controlling the level of behavioral responding [3-7]. However, the way in which interoceptive information related to physiological needs is integrated in the NAcC remains to be clarified. Located in the lateral and perifornical hypothalamic regions, orexin neurons [8, 9] are implicated in a wide range of functions, including arousal, feeding, and reward seeking [10-16]. Paraventricular thalamus (PVT) neurons receive a strong orexinergic projection [17] and are excited by orexins [18-20]. Hence, Kelley et al. [21] proposed that the PVT serves as an integrative relay, conveying hypothalamic energy-balance information to the NAc through its glutamatergic projection. Here, we test whether NAcC encoding of reward-predictive cues is modulated by the integration of posterior PVT (pPVT) orexin-mediated hunger-related signals. Using a cue-driven reward-seeking task, we show that satiety decreases cue responses in NAcC and pPVT neurons. Blockade of pPVT orexin-2 receptors reduces responding in hungry rats. Activation of pPVT neurons, either with local infusion of orexin-A or via optogenetics, positively controls NAcC cue responses and restores behavioral responding in sated rats, highlighting a circuit that integrates reward-predictive cues perceived in the environment with the current metabolic state of the animal.