Chapter 5 - Paraventricular thalamus: Gateway to feeding, appetitive motivation, and drug addiction

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Abstract

This chapter reviews the anatomical and functional evidence demonstrating the contribution of the paraventricular thalamic nucleus (PVT) to appetitive motivation, food intake control, and drug-seeking behaviors. We first consider the anatomical properties of the PVT to highlight its relevance in the control of appetitive motivation, feeding, and drug seeking. This is followed by a review of the available literature on PVT neurocircuitry, PVT involvement in food intake control, animal models of drug self-administration, withdrawal, and relapse. We show that PVT occupies a strategic position as a major thalamic interface between hindbrain and hypothalamic regions for viscerosensation and energy states; and between amygdala, cortical, and ventral striatal regions for motivation, reward, and learning. Understanding the precise anatomical and functional organization of these trans-PVT pathways remains a key challenge. Nonetheless, we show that PVT may be profitably viewed as the thalamic gateway to appetitive motivation, feeding, and drug addiction allowing both bottom-up (from brainstem and hypothalamus) and top-down (from cortex) control over reward and motivation.

Introduction

It has become increasingly clear that drugs of abuse and highly palatable foods share common neural signaling mechanisms that may underpin loss of control over intake and promote a persistent propensity to relapse to maladaptive patterns of ingestion and self-administration (Volkow and Wise, 2005, Volkow et al., 2012). Investigations into the overlapping circuits between drugs and foods provide compelling evidence for roles of the nucleus accumbens (Acb) and ventral tegmental area (VTA), key parts of the mammalian “reward circuitry,” as well as dopamine signaling in drug and food reward. Although these brain areas have been the focus in addiction and obesity research, the rise in novel technologies and sophisticated techniques has allowed researchers to further interrogate the reward system by characterizing the afferents and efferents that influence the function of the reward circuitry. One such input to the reward system, specifically the Acb, that is receiving more attention recently, is the paraventricular thalamic nucleus (PVT).

PVT is a midline thalamic nucleus that has extensive connections with forebrain, midbrain, and hindbrain regions. Although early intracranial self-stimulation studies hinted at a role for PVT in motivated behavior (Clavier and Gerfen, 1982, Cooper and Taylor, 1967), this role was for many years largely overlooked, with PVT function designated as having nonspecific functions of arousal due to its wide connectivity throughout the brain (Groenewegen and Berendse, 1994). However, within the past 10 years, there is renewed interest in the understanding of PVT function, particularly given its interactions with brain regions implicated in motivation, reward, and energy balance control, including Acb, amygdala, hypothalamus (Vertes and Hoover, 2008). In animal models of drug addiction literature, the recent surge in evidence supporting PVT as an important node in the circuitries for drug self-administration and relapse has led to the suggestion that PVT should be considered part of the drug addiction reward circuitry (Hamlin et al., 2009, James and Dayas, 2013, Martin-Fardon and Boutrel, 2012). However, the role of the PVT is broader and far more interesting still. PVT is also part of the hypothalamic–thalamic–striatal circuitry that acts to integrate information related to energy states and arousal to control feeding behaviors (Kelley et al., 2005). The PVT also serves important roles in aversive motivation and the interested reader is referred to Kirouac (2015) for review of this aspect of PVT function.

Here, we review the anatomical and functional evidence demonstrating the contribution of PVT neurons in appetitive motivation, food intake control, and drug-seeking behaviors. We start by considering the anatomical properties of the PVT to highlight its relevance in the control of appetitive motivation, feeding, and drug-related behaviors. This is followed by a review of the available literature in animal models on PVT function, specifically focusing on PVT neurocircuitry and their involvement in food intake control, drug taking and relapse. A list of abbreviations used in this report is provided in Table 1.

PVT occupies a strategic position as the major thalamic interface between hindbrain and hypothalamic regions for viscerosensation and energy states; and between amygdala, cortical, and ventral striatal regions for motivation, reward, and learning. In this way, PVT is a thalamic gateway to appetitive motivation, feeding, and drug addiction allowing both bottom-up (from brainstem and hypothalamus) and top-down (from cortex) control over striatal and extended amygdala circuitries for reward and motivation.

Section snippets

Anatomical Organization of the PVT Within a Motivational Framework

The PVT is the dorsal member of the midline thalamic nuclei. Although modest in its dorsoventral dimension, it is notably extensive along the anterior–posterior axis of the thalamus, lining the bottom of the third ventricle. It has both anterior (aPVT) and posterior (pPVT) subdivisions; aPVT is bounded between paratenial nuclei, whereas pPVT is bordered by the mediodorsal thalamus; the functional significance of this division is discussed here on the basis of segregated outputs from these

PVT and Appetitive Motivation

More than a decade ago, Ann Kelley and colleagues proposed a role for the PVT in the control of feeding behaviors (Kelley, 2004). This suggestion was based, in part, on the patterns of anatomical connectivity described earlier, placing the PVT as the thalamic interface between hindbrain and hypothalamic regions for viscerosensation as well as energy states; and amygdala, cortical, and ventral striatal regions for motivation, reward, and learning. However, for many years, the contribution of the

PVT in Drug Taking, Withdrawal, and Relapse

The PVT is anatomically well placed to contribute to various aspects of the reinforcing effects of drugs of abuse as well as to relapse to drug seeking. Each of the major PVT efferents reviewed previously (PL, IL, BLA, AcbSh) contribute to drug self-administration or relapse to drug seeking (James and Dayas, 2013, Khoo et al., 2016) and hypothalamic inputs to PVT have been implicated in this self-administration and relapse (Khoo et al., 2016). Indeed, several authors have noted the key

Conclusions

Here, we have reviewed the anatomical and functional evidence for the roles of the PVT in appetitive motivation, food intake control, and drug-motivated behaviors. From the evidence considered here, it is clear that the PVT occupies a strategic position as a major thalamic interface that communicates information on viscerosensation as well as energy states to modulate behaviors related to motivation, reward, and learning. The neural mechanisms mediating these roles of PVT neurons are still

Acknowledgments

Preparation of this manuscript was supported by grants from the Australian Research Council (DP170100075, DP160100004) and the National Health and Medical Research Council (GNT1098436, GNT1077806, GNT1077804) to G.P.M. and an Australian Research Council DECRA (DE170101384) to Z.Y.O.

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