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Hunger neurons drive feeding through a sustained, positive reinforcement signal

View Article: PubMed Central - PubMed

ABSTRACT

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

Doi:: http://dx.doi.org/10.7554/eLife.18640.001

No MeSH data available.


Related in: MedlinePlus

Prestimulation of AgRP neurons primes feeding.(A–B) 60 min food intake of (A) AgRP-ChR2 (n = 5) and (B) WT control (n = 4) mice in trials conducted in consecutive days. (C) Analysis of 60 min food intake of AgRP-ChR2 (n = 5) and WT control (n = 4) mice under different stimulation condition. Asterisks indicate the significance level for comparison between WT and AgRP:ChR2 animals subjected to same stimulation protocol. ns, not significant. (D) Average 60 min food intake evoked by prestimulation with a varied temporal structure of laser pulses (n = 8 Asterisks on top of bar plots indicate significance levels compared to no stimulation control and asterisks on top of brackets indicate significance levels for comparisons with the respective protocols, using one-way-ANOVA with Holm-Sidak’s correction for multiple comparisons (****p≤0.0001, ***0.0001<p≤0.001, **0.001<p≤0.01, *0.01<p≤0.05, ns p>0.05).DOI:http://dx.doi.org/10.7554/eLife.18640.003
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fig1s1: Prestimulation of AgRP neurons primes feeding.(A–B) 60 min food intake of (A) AgRP-ChR2 (n = 5) and (B) WT control (n = 4) mice in trials conducted in consecutive days. (C) Analysis of 60 min food intake of AgRP-ChR2 (n = 5) and WT control (n = 4) mice under different stimulation condition. Asterisks indicate the significance level for comparison between WT and AgRP:ChR2 animals subjected to same stimulation protocol. ns, not significant. (D) Average 60 min food intake evoked by prestimulation with a varied temporal structure of laser pulses (n = 8 Asterisks on top of bar plots indicate significance levels compared to no stimulation control and asterisks on top of brackets indicate significance levels for comparisons with the respective protocols, using one-way-ANOVA with Holm-Sidak’s correction for multiple comparisons (****p≤0.0001, ***0.0001<p≤0.001, **0.001<p≤0.01, *0.01<p≤0.05, ns p>0.05).DOI:http://dx.doi.org/10.7554/eLife.18640.003

Mentions: To test the hypothesis that AgRP neurons drive feeding through a sustained mechanism, we used optogenetics to manipulate AgRP neuron activity before food presentation and then measured the effect on subsequent feeding behavior (Figure 1B). Ad libitum fed mice expressing channelrhodopsin in AgRP neurons (AgRP-ChR2; Figure 1C) were acclimated to a behavioral chamber early in the light phase, a time when mice ordinarily eat little, and photostimulated for one hour in the absence of food. Photostimulation was then terminated and food was made available (Figure 1B). Strikingly, we found that this preparatory photostimulation triggered intense feeding upon subsequent food presentation (Figure 1D–G). This voracious feeding approached the level of food consumption observed following an overnight fast (Figure 1E); it did not require learning, as it was observed in the first trial of every mouse (Figure 1—figure supplement 1); and it was absent from control mice that lacked ChR2 expression (Figure 1—figure supplement 1). Thus stimulation of AgRP neurons in the absence of food is sufficient to elicit intense food consumption at a later time when food is made available. Importantly, this observation provides an explanation for how AgRP neurons can promote feeding despite being inhibited at a meal’s outset by the sensory detection of food (Figure 1A).10.7554/eLife.18640.002Figure 1.Prestimulation of AgRP neurons promotes sustained consummatory behavior.


Hunger neurons drive feeding through a sustained, positive reinforcement signal
Prestimulation of AgRP neurons primes feeding.(A–B) 60 min food intake of (A) AgRP-ChR2 (n = 5) and (B) WT control (n = 4) mice in trials conducted in consecutive days. (C) Analysis of 60 min food intake of AgRP-ChR2 (n = 5) and WT control (n = 4) mice under different stimulation condition. Asterisks indicate the significance level for comparison between WT and AgRP:ChR2 animals subjected to same stimulation protocol. ns, not significant. (D) Average 60 min food intake evoked by prestimulation with a varied temporal structure of laser pulses (n = 8 Asterisks on top of bar plots indicate significance levels compared to no stimulation control and asterisks on top of brackets indicate significance levels for comparisons with the respective protocols, using one-way-ANOVA with Holm-Sidak’s correction for multiple comparisons (****p≤0.0001, ***0.0001<p≤0.001, **0.001<p≤0.01, *0.01<p≤0.05, ns p>0.05).DOI:http://dx.doi.org/10.7554/eLife.18640.003
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fig1s1: Prestimulation of AgRP neurons primes feeding.(A–B) 60 min food intake of (A) AgRP-ChR2 (n = 5) and (B) WT control (n = 4) mice in trials conducted in consecutive days. (C) Analysis of 60 min food intake of AgRP-ChR2 (n = 5) and WT control (n = 4) mice under different stimulation condition. Asterisks indicate the significance level for comparison between WT and AgRP:ChR2 animals subjected to same stimulation protocol. ns, not significant. (D) Average 60 min food intake evoked by prestimulation with a varied temporal structure of laser pulses (n = 8 Asterisks on top of bar plots indicate significance levels compared to no stimulation control and asterisks on top of brackets indicate significance levels for comparisons with the respective protocols, using one-way-ANOVA with Holm-Sidak’s correction for multiple comparisons (****p≤0.0001, ***0.0001<p≤0.001, **0.001<p≤0.01, *0.01<p≤0.05, ns p>0.05).DOI:http://dx.doi.org/10.7554/eLife.18640.003
Mentions: To test the hypothesis that AgRP neurons drive feeding through a sustained mechanism, we used optogenetics to manipulate AgRP neuron activity before food presentation and then measured the effect on subsequent feeding behavior (Figure 1B). Ad libitum fed mice expressing channelrhodopsin in AgRP neurons (AgRP-ChR2; Figure 1C) were acclimated to a behavioral chamber early in the light phase, a time when mice ordinarily eat little, and photostimulated for one hour in the absence of food. Photostimulation was then terminated and food was made available (Figure 1B). Strikingly, we found that this preparatory photostimulation triggered intense feeding upon subsequent food presentation (Figure 1D–G). This voracious feeding approached the level of food consumption observed following an overnight fast (Figure 1E); it did not require learning, as it was observed in the first trial of every mouse (Figure 1—figure supplement 1); and it was absent from control mice that lacked ChR2 expression (Figure 1—figure supplement 1). Thus stimulation of AgRP neurons in the absence of food is sufficient to elicit intense food consumption at a later time when food is made available. Importantly, this observation provides an explanation for how AgRP neurons can promote feeding despite being inhibited at a meal’s outset by the sensory detection of food (Figure 1A).10.7554/eLife.18640.002Figure 1.Prestimulation of AgRP neurons promotes sustained consummatory behavior.

View Article: PubMed Central - PubMed

ABSTRACT

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how these cells can promote feeding at all. Here we resolve this paradox by showing that brief optogenetic stimulation of AgRP neurons before food availability promotes intense appetitive and consummatory behaviors that persist for tens of minutes in the absence of continued AgRP neuron activation. We show that these sustained behavioral responses are mediated by a long-lasting potentiation of the rewarding properties of food and that AgRP neuron activity is positively reinforcing. These findings reveal that hunger neurons drive feeding by transmitting a positive valence signal that triggers a stable transition between behavioral states.

Doi:: http://dx.doi.org/10.7554/eLife.18640.001

No MeSH data available.


Related in: MedlinePlus