The Paraventricular Thalamus as a Critical Node of Motivated Behavior via the Hypothalamic-Thalamic-Striatal Circuit

Abstract

In this review, we highlight evidence that supports a role for the paraventricular nucleus of the thalamus (PVT) in motivated behavior. We include a neuroanatomical and neurochemical overview, outlining what is known of the cellular makeup of the region and its most prominent afferent and efferent connections. We discuss how these connections and distinctions across the anterior-posterior axis correspond to the perceived function of the PVT. We then focus on the hypothalamic-thalamic-striatal circuit and the neuroanatomical and functional placement of the PVT within this circuit. In this regard, the PVT is ideally positioned to integrate information regarding internal states and the external environment and translate it into motivated actions. Based on data that has emerged in recent years, including that from our laboratory, we posit that orexinergic (OX) innervation from the lateral hypothalamus (LH) to the PVT encodes the incentive motivational value of reward cues and thereby alters the signaling of the glutamatergic neurons projecting from the PVT to the shell of the nucleus accumbens (NAcSh). The PVT-NAcSh pathway then modulates dopamine activity and resultant cue-motivated behaviors. As we and others apply novel tools and approaches to studying the PVT we will continue to refine the anatomical, cellular, and functional definitions currently ascribed to this nucleus and further elucidate its role in motivated behaviors.

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress-related contexts

“…Although we cannot rule out yet whether and how the adaptive activation of PVT-neurons following TH deletion may be responsible for the direct activation of LH and DMH regions, it is interesting to note that PVT excitatory (glutamate) neurons also project to the hypothalamus 29,76 , therefore potentially modulating feeding and energy homeostasis. Indeed, while the existence of a hypothalamu→PV→accumbal circuit seems critical for behavioral adaptations 7,26,29,77–80 , our results combined to previous and recent literature 8,16,17,76,81 also suggest a hindbrai→PV→hypothalamus path that may regulate homeostatic functions requiring the integration of exteroceptive and interoceptive signals.…”

“…However, we cannot formally exclude that the partial loss of hindbrain TH-neurons may impact on the hypothalamic activity in virtue of other circuits (hindbrain TH →hypothalamus and/or hindbrain TH →PBN→hypothalamus paths). Indeed, while the existence of a hypothalamus→PVT→accumbal circuit seems critical for behavioral adaptations (Betley et al ., 2013; Zhang & van den Pol, 2017; Otis et al ., 2019; Meffre et al ., 2019; Zhang et al ., 2020; Iglesias & Flagel, 2021; Engelke et al ., 2021), our results, together with previous and recent literature (Otake et al ., 1994; Ong et al ., 2017; Beas et al ., 2018; Sofia Beas et al ., 2020; Li et al ., 2021), also suggest a hindbrain→PVT→hypothalamus path that may regulate homeostatic functions requiring the integration of exteroceptive and interoceptive signals.…”

Hindbrain catecholaminergic inputs to the paraventricular thalamus scale feeding and metabolic efficiency in stress‐related contexts

“…However, we cannot formally exclude the possibility that the partial loss of hindbrain TH neurons may impact on the hypothalamic activity in virtue of other circuits (hindbrain TH →hypothalamus and/or hindbrain TH →parabrachial nucleusparabrachial nucleus→hypothalamus paths). Indeed, although the existence of a hypothalamus→PVT→accumbal circuit appears to be critical for behavioural adaptations (Betley et al., 2013; Engelke et al., 2021; Iglesias & Flagel, 2021; Meffre et al., 2019; Otis et al., 2019; Zhang & van den Pol, 2017; Zhang et al., 2020), our results, together with previous and recent literature (Beas et al., 2018; Li et al., 2021; Ong et al., 2017; Otake et al., 1994; Sofia Beas et al., 2020), also suggest a hindbrain→PVT→hypothalamus path that may regulate homeostatic functions requiring the integration of exteroceptive and interoceptive signals.…”

Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of thalamus

“…PVT is involved in multiple behaviors such as fear memory (Do-Monte et al, 2015; Penzo et al, 2015), reward-seeking (Do-Monte et al, 2017; Keyes et al, 2020; Otis et al, 2017; Otis et al, 2019; Zhu et al, 2016), food intake (Horio and Liberles, 2021; Meffre et al, 2019; Zhang and van den Pol, 2017), and sociability (Yamamuro et al, 2020). PVT also mediates emotion (Kasahara et al, 2016; Kato et al, 2019), saliency (Zhu et al, 2018), and wakefulness (Ren et al, 2018) and therefore assumed as a crucial brain network node/hub for motivated behaviors (Iglesias and Flagel, 2021), anxiety (Kirouac, 2021), and behavior homeostasis (Penzo and Gao, 2021).…”