Decoding Neural Circuits that Control Compulsive Sucrose Seeking

Abstract

The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces “compulsive” sucrose-seeking, but not food consumption in hungry mice. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feeding-related behavior. Our study overlays information about the type, function and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.

Lateral Hypothalamus GABAergic Neurons Modulate Consummatory Behaviors Regardless of the Caloric Content or Biological Relevance of the Consumed Stimuli

“…Additional research is necessary to confirm the potential role of LH to NAc GABAergic pathways in the modulation of reward consumption. Interestingly, activation of a VTA-projecting GABAergic pathway was recently shown to increase food intake and aberrant gnawing behaviors (Nieh et al, 2015), which is also a possible pathway underlying the present observations.…”

Resolving the neural circuits of anxiety

“…Hypothalamic drives to maintain homeostasis (i.e., to seek and consume food or water 126,127 ) can also overwhelm threat avoidance and anxiety-like behaviors. Stimulation of lateral hypothalamic terminals in the VTA, for example, promotes sucrose seeking, even when mice must cross an electrified floor to obtain the sucrose reward 128 . Thus, subcortical motivational systems contribute to the evaluation of threat interpretations by shifting the balance toward appetitive behaviors and away from anxiety-like behaviors.…”

Eating behavior in frontotemporal dementia

“…32 Recent animal studies have also shown that the lateral hypothalamus connects to the reward centers in the ventral tegmental area, which may mediate sucrose preference. 33 The hypothalamus is therefore densely connected to many of the areas involved in reward processing that may also influence eating behaviors. 32 Many of these brain regions also undergo pathologic changes in bvFTD, 32,34 potentially disrupting reward feedback between these centers and the hypothalamus, leading to changes in eating behavior.…”