Three Pillars for the Neural Control of Appetite

Abstract

The neural control of appetite is important for understanding motivated behavior as well as the present rising prevalence of obesity. Over the past several years, new tools for cell type-specific neuron activity monitoring and perturbation have enabled increasingly detailed analyses of the mechanisms underlying appetite-control systems. Three major neural circuits strongly and acutely influence appetite but with notably different characteristics. Although these circuits interact, they have distinct properties and thus appear to contribute to separate but interlinked processes influencing appetite, thereby forming three pillars of appetite control. Here, we summarize some of the key characteristics of appetite circuits that are emerging from recent work and synthesize the findings into a provisional framework that can guide future studies.

Toward a Wiring Diagram Understanding of Appetite Control

“…In this way, the magnitude of the rapid drop in AgRP neuron activity following cues predicting upcoming food consumption may reflect the expected reduction in energy deficit once this immediately available food is consumed, digested, and absorbed. Consistent with this view, when food consumption instead consists of several small meals, each anticipated to be less than that required to restore energy homeostasis (Figure 10B,C), AgRP firing undergoes successive drops to lower firing levels (Betley et al, 2015; Chen et al, 2015; Livneh et al, 2017; Sternson and Eiselt, 2017). Consumption of even smaller quantities of food, each replenishing only a tiny fraction of the total energy deficit (as is the case during many operant behavioral tasks) results in AgRP activity remaining elevated (Figure 10C), with only slight drops following food detection (Livneh et al, 2017).…”

“…A complementary role for rapid changes in AgRP neuron activity was proposed by Sternson and colleagues (Betley et al, 2015; Sternson and Eiselt, 2017). These authors found that AgRP neuron stimulation was mildly aversive, and suggest that the drop in AgRP activity may provide rapid relief from this aversive state and act as a teaching signal to reinforce learning of cues predicting food (but see (Chen et al, 2016) for an alternative interpretation).…”

“…Many hypotheses have been put forward (Betley et al, 2015; Chen and Knight, 2016; Chen et al, 2015; Mandelblat-Cerf et al, 2015; Seeley and Berridge, 2015; Sternson and Eiselt, 2017). Below, we review evidence that the brain does not typically drive foraging in response to hormonal ‘feedback’ signals of acute energy deficit.…”

“…Prevailing evidence would seem to favor the latter. See (Sternson and Eiselt, 2017) for excellent coverage of the contributions of LH to the regulation of feeding-related behaviors.ARC → PVH → LPBN → ? → ?…”

Definition of the hypothalamic GnRH pulse generator in mice

“…These events are not detected by current pulse analysis algorithms, and indicate the need for the further development of LH pulse analysis methodologies. In terms of ARN function, it is intriguing to find a 10-min neuronal oscillator embedded among ARN neural circuitries subserving longer-term functions such as feeding initiation (29). With evidence for kisspeptin inputs into these feeding circuits and others (30), it will be interesting to examine the impact of this fast oscillator on other ARN outputs in future studies.…”