Aitken, T. J. | Search bioRxiv

bioRxiv2023

Negative feedback control of hunger circuits by the taste of food

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here we show that hunger-promoting AgRP neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin receptor-expressing neurons in the dorsomedial hypothalamus (DMHLepR) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption.

neuroscience↗

bioRxiv2019

Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

BackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.\n\nMethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.\n\nResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of {beta}2-containing nicotinic acetylcholine receptors.\n\nConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.

neuroscience↗