Homeostatic circuits selectively gate food cue responses in insular cortex

Abstract

Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food- cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues.

Toward a Wiring Diagram Understanding of Appetite Control

“…In this sense, AgRP neurons and the wiring diagram within which they operate can be viewed as the physical embodiment of the intervening variable , hunger. Consistent with this, as alluded to in Figure 1, activation of AgRP neurons induces many of the behavioral effects associated with hunger (Aponte et al, 2011; Burnett et al, 2016; Krashes et al, 2011; Livneh et al, 2017). …”

“…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).…”

“…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). In all cases, the residual AgRP firing immediately following consumption would likely drive subsequent foraging, albeit with reduced vigor (Aponte et al, 2011).…”

“…We recently tested this hypothesis directly, by establishing a chronic cellular-resolution imaging platform in behaving mice for evaluating hunger-dependent processing of learned food cues (i) in the same individual cortical neurons across slowly changing states of natural hunger and satiety, and (ii) during selective chemogenetic activation of AgRP neurons (Livneh et al, 2017). Food-restricted mice were trained to lick following presentation of a visual food cue in order to obtain a highly palatable food reward, and to avoid licking to other cues to avoid delivery of quinine, an aversive tastant (Burgess et al, 2016; Livneh et al, 2017).…”

Economic Choice as an Untangling of Options into Actions

“…Livneh et al, 2017). Then the information processed in specialized regions such as insular cortex may combine with form vision information (‘red apple and brown peanuts’).…”