Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning

Melissa J Sharpe, Nathan J Marchant, Leslie R Whitaker, Christopher T Richie, Yajun J Zhang, Erin J Campbell, Pyry P Koivula, Julie C Necarsulmer, Carlos Mejias-Aponte, Marisela Morales, James Pickel, Jeffrey C Smith, Yael Niv, Yavin Shaham, Brandon K Harvey, Geoffrey Schoenbaum

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors. However, these effects could also reflect the storage of associative information about the cues leading to food in LH itself. Here, we present data from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.

Original languageEnglish
Pages (from-to)2089-2100.e5
JournalCurrent Biology
Volume27
Issue number14
DOIs
Publication statusPublished - 24 Jul 2017

Cite this

Sharpe, Melissa J ; Marchant, Nathan J ; Whitaker, Leslie R ; Richie, Christopher T ; Zhang, Yajun J ; Campbell, Erin J ; Koivula, Pyry P ; Necarsulmer, Julie C ; Mejias-Aponte, Carlos ; Morales, Marisela ; Pickel, James ; Smith, Jeffrey C ; Niv, Yael ; Shaham, Yavin ; Harvey, Brandon K ; Schoenbaum, Geoffrey. / Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning. In: Current Biology. 2017 ; Vol. 27, No. 14. pp. 2089-2100.e5.
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abstract = "Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors. However, these effects could also reflect the storage of associative information about the cues leading to food in LH itself. Here, we present data from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.",
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author = "Sharpe, {Melissa J} and Marchant, {Nathan J} and Whitaker, {Leslie R} and Richie, {Christopher T} and Zhang, {Yajun J} and Campbell, {Erin J} and Koivula, {Pyry P} and Necarsulmer, {Julie C} and Carlos Mejias-Aponte and Marisela Morales and James Pickel and Smith, {Jeffrey C} and Yael Niv and Yavin Shaham and Harvey, {Brandon K} and Geoffrey Schoenbaum",
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Sharpe, MJ, Marchant, NJ, Whitaker, LR, Richie, CT, Zhang, YJ, Campbell, EJ, Koivula, PP, Necarsulmer, JC, Mejias-Aponte, C, Morales, M, Pickel, J, Smith, JC, Niv, Y, Shaham, Y, Harvey, BK & Schoenbaum, G 2017, 'Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning' Current Biology, vol. 27, no. 14, pp. 2089-2100.e5. https://doi.org/10.1016/j.cub.2017.06.024

Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning. / Sharpe, Melissa J; Marchant, Nathan J; Whitaker, Leslie R; Richie, Christopher T; Zhang, Yajun J; Campbell, Erin J; Koivula, Pyry P; Necarsulmer, Julie C; Mejias-Aponte, Carlos; Morales, Marisela; Pickel, James; Smith, Jeffrey C; Niv, Yael; Shaham, Yavin; Harvey, Brandon K; Schoenbaum, Geoffrey.

In: Current Biology, Vol. 27, No. 14, 24.07.2017, p. 2089-2100.e5.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Lateral Hypothalamic GABAergic Neurons Encode Reward Predictions that Are Relayed to the Ventral Tegmental Area to Regulate Learning

AU - Sharpe, Melissa J

AU - Marchant, Nathan J

AU - Whitaker, Leslie R

AU - Richie, Christopher T

AU - Zhang, Yajun J

AU - Campbell, Erin J

AU - Koivula, Pyry P

AU - Necarsulmer, Julie C

AU - Mejias-Aponte, Carlos

AU - Morales, Marisela

AU - Pickel, James

AU - Smith, Jeffrey C

AU - Niv, Yael

AU - Shaham, Yavin

AU - Harvey, Brandon K

AU - Schoenbaum, Geoffrey

N1 - Published by Elsevier Ltd.

PY - 2017/7/24

Y1 - 2017/7/24

N2 - Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors. However, these effects could also reflect the storage of associative information about the cues leading to food in LH itself. Here, we present data from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.

AB - Eating is a learned process. Our desires for specific foods arise through experience. Both electrical stimulation and optogenetic studies have shown that increased activity in the lateral hypothalamus (LH) promotes feeding. Current dogma is that these effects reflect a role for LH neurons in the control of the core motivation to feed, and their activity comes under control of forebrain regions to elicit learned food-motivated behaviors. However, these effects could also reflect the storage of associative information about the cues leading to food in LH itself. Here, we present data from several studies that are consistent with a role for LH in learning. In the first experiment, we use a novel GAD-Cre rat to show that optogenetic inhibition of LH γ-aminobutyric acid (GABA) neurons restricted to cue presentation disrupts the rats' ability to learn that a cue predicts food without affecting subsequent food consumption. In the second experiment, we show that this manipulation also disrupts the ability of a cue to promote food seeking after learning. Finally, we show that inhibition of the terminals of the LH GABA neurons in ventral-tegmental area (VTA) facilitates learning about reward-paired cues. These results suggest that the LH GABA neurons are critical for storing and later disseminating information about reward-predictive cues.

KW - Journal Article

U2 - 10.1016/j.cub.2017.06.024

DO - 10.1016/j.cub.2017.06.024

M3 - Article

VL - 27

SP - 2089-2100.e5

JO - Current Biology

JF - Current Biology

SN - 0960-9822

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