Limits...
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

AgRP neurons support positive, but not negative, reinforcement.(A) Schematic of the negative reinforcement protocol that tests whether animals will lever press to shut off AgRP neuron activity. (B) Number of presses for the active and inactive lever in a 60 min negative reinforcement test (n = 6). (C) Induction of Fos expression in AgRP neurons of mice that are allowed to self-stimulate by lever pressing (top), but not in mice in which the lever has been disconnected from the laser (bottom). (D) Quantification of the percentage of AgRP neurons that express Fos in each group (n = 3). Asterisks indicate a significant difference in Fos expression between the two groups by an unpaired, two-tailed t-test. (**0.001<p≤0.01).DOI:http://dx.doi.org/10.7554/eLife.18640.010
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5016090&req=5

fig6s1: AgRP neurons support positive, but not negative, reinforcement.(A) Schematic of the negative reinforcement protocol that tests whether animals will lever press to shut off AgRP neuron activity. (B) Number of presses for the active and inactive lever in a 60 min negative reinforcement test (n = 6). (C) Induction of Fos expression in AgRP neurons of mice that are allowed to self-stimulate by lever pressing (top), but not in mice in which the lever has been disconnected from the laser (bottom). (D) Quantification of the percentage of AgRP neurons that express Fos in each group (n = 3). Asterisks indicate a significant difference in Fos expression between the two groups by an unpaired, two-tailed t-test. (**0.001<p≤0.01).DOI:http://dx.doi.org/10.7554/eLife.18640.010

Mentions: The preceding data suggest that AgRP neurons transmit a long-lasting, positive valence signal that potentiates the incentive value of food. The effect of this mechanism is to transform AgRP neuron firing before food availability into a sustained drive that can motivate feeding later. An important question is whether this positive valence mechanism is sufficiently strong to account for the dramatic instrumental responses (e.g. lever pressing, nose poking) that animals exhibit following AgRP neuron activation. Of note, a previous study reported that mice failed to perform operant responses in order to shut off AgRP neuron activity, indicating that these neurons do not motivate behavior by negative reinforcement (Betley et al., 2015), which we confirmed independently (Figure 6—figure supplement 1). However whether mice will perform these same actions in order to turn on AgRP neuron activity has never been tested.


Hunger neurons drive feeding through a sustained, positive reinforcement signal
AgRP neurons support positive, but not negative, reinforcement.(A) Schematic of the negative reinforcement protocol that tests whether animals will lever press to shut off AgRP neuron activity. (B) Number of presses for the active and inactive lever in a 60 min negative reinforcement test (n = 6). (C) Induction of Fos expression in AgRP neurons of mice that are allowed to self-stimulate by lever pressing (top), but not in mice in which the lever has been disconnected from the laser (bottom). (D) Quantification of the percentage of AgRP neurons that express Fos in each group (n = 3). Asterisks indicate a significant difference in Fos expression between the two groups by an unpaired, two-tailed t-test. (**0.001<p≤0.01).DOI:http://dx.doi.org/10.7554/eLife.18640.010
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016090&req=5

fig6s1: AgRP neurons support positive, but not negative, reinforcement.(A) Schematic of the negative reinforcement protocol that tests whether animals will lever press to shut off AgRP neuron activity. (B) Number of presses for the active and inactive lever in a 60 min negative reinforcement test (n = 6). (C) Induction of Fos expression in AgRP neurons of mice that are allowed to self-stimulate by lever pressing (top), but not in mice in which the lever has been disconnected from the laser (bottom). (D) Quantification of the percentage of AgRP neurons that express Fos in each group (n = 3). Asterisks indicate a significant difference in Fos expression between the two groups by an unpaired, two-tailed t-test. (**0.001<p≤0.01).DOI:http://dx.doi.org/10.7554/eLife.18640.010
Mentions: The preceding data suggest that AgRP neurons transmit a long-lasting, positive valence signal that potentiates the incentive value of food. The effect of this mechanism is to transform AgRP neuron firing before food availability into a sustained drive that can motivate feeding later. An important question is whether this positive valence mechanism is sufficiently strong to account for the dramatic instrumental responses (e.g. lever pressing, nose poking) that animals exhibit following AgRP neuron activation. Of note, a previous study reported that mice failed to perform operant responses in order to shut off AgRP neuron activity, indicating that these neurons do not motivate behavior by negative reinforcement (Betley et al., 2015), which we confirmed independently (Figure 6—figure supplement 1). However whether mice will perform these same actions in order to turn on AgRP neuron activity has never been tested.

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