Lateral Hypothalamic Control of the Ventral Tegmental Area: Reward Evaluation and the Driving of Motivated Behavior

Abstract

The lateral hypothalamus (LH) plays an important role in many motivated behaviors, sleep-wake states, food intake, drug-seeking, energy balance, etc. It is also home to a heterogeneous population of neurons that express and co-express multiple neuropeptides including hypocretin (Hcrt), melanin-concentrating hormone (MCH), cocaine- and amphetamine-regulated transcript (CART) and neurotensin (NT). These neurons project widely throughout the brain to areas such as the locus coeruleus, the bed nucleus of the stria terminalis, the amygdala and the ventral tegmental area (VTA). Lateral hypothalamic projections to the VTA are believed to be important for driving behavior due to the involvement of dopaminergic reward circuitry. The purpose of this article is to review current knowledge regarding the lateral hypothalamic connections to the VTA and the role they play in driving these behaviors.

Efferent projections of excitatory and inhibitory preBötzinger Complex neurons

“…Lateral and dorsomedial hypothalamus . These structures are implicated in feeding, reward, sleep/wakefulness, circadian rhythm, and stress (Saper, ; Stuber & Wise, ; Tyree & de Lecea, ). They contain orexin‐producing neurons, some sensitive to CO 2 and pH (Williams, Jensen, Verkhratsky, Fugger, & Burdakov, ), that affect breathing across different states of arousal (Williams & Burdakov, ).…”

“…Lateral and dorsomedial hypothalamus. These structures are implicated in feeding, reward, sleep/wakefulness, circadian rhythm, and stress (Saper, 2006;Stuber & Wise, 2016;Tyree & de Lecea, 2017).…”

Blunted leptin sensitivity during hedonic overeating can be reinstated by activating galanin 2 receptors (Gal2R) in the lateral hypothalamus

“…43 The fact that the LHA innervates the VTA, an important driver of motivated behaviour, [44][45][46] also suggests that this hypothalamic nucleus plays a key role in regulating the intake of hedonic foods. 43 The fact that the LHA innervates the VTA, an important driver of motivated behaviour, [44][45][46] also suggests that this hypothalamic nucleus plays a key role in regulating the intake of hedonic foods.…”

“…The lateral hypothalamic area (LHA), a brain area that plays a key role in the integration of hedonic and homeostatic information, is responsive to both, ghrelin and leptin. 43 The fact that the LHA innervates the VTA, an important driver of motivated behaviour, [44][45][46] also suggests that this hypothalamic nucleus plays a key role in regulating the intake of hedonic foods. In support of the latter view, we found that access to hedonic food increases neuronal activity in the LHA, as well as other areas responsible for processing reward/hedonic and/ or homeostatic signals.…”

Unravelling the role and mechanism of adipokine and gastrointestinal signals in animal models in the nonhomeostatic control of energy homeostasis: Implications for binge eating disorder

“…The lateral hypothalamic area (LHA) historically treated as a "feeding centre" acts as a hub for the integration of diverse central and peripheral signals and coordinates adaptive behavioural responses to the environment (Berthoud & Munzberg, 2011;Bonnavion, Mickelsen, Fujita, de Lecea, & Jackson, 2016). Likewise, it has been postulated as the crucial link between homeostatic and hedonic aspects of food intake behaviour (Stuber & Wise, 2016;Tyree & de Lecea, 2017). In fact, the LHA projects densely to the VTA and acts on its dopaminergic neurons, suggesting that both structures are relevant for driving goal-orientated behaviours.…”