Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards

Kayoko W. Miyazaki, Katsuhiko Miyazaki, Kenji Tanaka, Akihiro Yamanaka, Aki Takahashi, Sawako Tabuchi, Kenji Doya

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals patience to wait for a delayed reward.

Original languageEnglish
Pages (from-to)2033-2040
Number of pages8
JournalCurrent Biology
Volume24
Issue number17
DOIs
Publication statusPublished - 2014 Sep 8

Fingerprint

Optogenetics
Reward
serotonin
Neurons
Serotonin
neurons
Chemical activation
Animals
Cues
brain
Serotonergic Neurons
Dorsal Raphe Nucleus
optogenetics
animals
Animal Behavior
Impulsive Behavior
Therapeutic Uses
neurotransmitters
Arousal
dopamine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Miyazaki, K. W., Miyazaki, K., Tanaka, K., Yamanaka, A., Takahashi, A., Tabuchi, S., & Doya, K. (2014). Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. Current Biology, 24(17), 2033-2040. https://doi.org/10.1016/j.cub.2014.07.041

Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. / Miyazaki, Kayoko W.; Miyazaki, Katsuhiko; Tanaka, Kenji; Yamanaka, Akihiro; Takahashi, Aki; Tabuchi, Sawako; Doya, Kenji.

In: Current Biology, Vol. 24, No. 17, 08.09.2014, p. 2033-2040.

Research output: Contribution to journalArticle

Miyazaki, KW, Miyazaki, K, Tanaka, K, Yamanaka, A, Takahashi, A, Tabuchi, S & Doya, K 2014, 'Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards', Current Biology, vol. 24, no. 17, pp. 2033-2040. https://doi.org/10.1016/j.cub.2014.07.041
Miyazaki, Kayoko W. ; Miyazaki, Katsuhiko ; Tanaka, Kenji ; Yamanaka, Akihiro ; Takahashi, Aki ; Tabuchi, Sawako ; Doya, Kenji. / Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards. In: Current Biology. 2014 ; Vol. 24, No. 17. pp. 2033-2040.
@article{58ef642295a34cc5a91372ed5f4ca00c,
title = "Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards",
abstract = "Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals patience to wait for a delayed reward.",
author = "Miyazaki, {Kayoko W.} and Katsuhiko Miyazaki and Kenji Tanaka and Akihiro Yamanaka and Aki Takahashi and Sawako Tabuchi and Kenji Doya",
year = "2014",
month = "9",
day = "8",
doi = "10.1016/j.cub.2014.07.041",
language = "English",
volume = "24",
pages = "2033--2040",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "17",

}

TY - JOUR

T1 - Optogenetic activation of dorsal raphe serotonin neurons enhances patience for future rewards

AU - Miyazaki, Kayoko W.

AU - Miyazaki, Katsuhiko

AU - Tanaka, Kenji

AU - Yamanaka, Akihiro

AU - Takahashi, Aki

AU - Tabuchi, Sawako

AU - Doya, Kenji

PY - 2014/9/8

Y1 - 2014/9/8

N2 - Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals patience to wait for a delayed reward.

AB - Serotonin is a neuromodulator that is involved extensively in behavioral, affective, and cognitive functions in the brain. Previous recording studies of the midbrain dorsal raphe nucleus (DRN) revealed that the activation of putative serotonin neurons correlates with the levels of behavioral arousal [1], rhythmic motor outputs [2], salient sensory stimuli [3-6], reward, and conditioned cues [5-8]. The classic theory on serotonin states that it opposes dopamine and inhibits behaviors when aversive events are predicted [9-14]. However, the therapeutic effects of serotonin signal-enhancing medications have been difficult to reconcile with this theory [15, 16]. In contrast, a more recent theory states that serotonin facilitates long-term optimal behaviors and suppresses impulsive behaviors [17-21]. To test these theories, we developed optogenetic mice that selectively express channelrhodopsin in serotonin neurons and tested how the activation of serotonergic neurons in the DRN affects animal behavior during a delayed reward task. The activation of serotonin neurons reduced the premature cessation of waiting for conditioned cues and food rewards. In reward omission trials, serotonin neuron stimulation prolonged the time animals spent waiting. This effect was observed specifically when the animal was engaged in deciding whether to keep waiting and was not due to motor inhibition. Control experiments showed that the prolonged waiting times observed with optogenetic stimulation were not due to behavioral inhibition or the reinforcing effects of serotonergic activation. These results show, for the first time, that the timed activation of serotonin neurons during waiting promotes animals patience to wait for a delayed reward.

UR - http://www.scopus.com/inward/record.url?scp=84907984161&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907984161&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2014.07.041

DO - 10.1016/j.cub.2014.07.041

M3 - Article

C2 - 25155504

AN - SCOPUS:84907984161

VL - 24

SP - 2033

EP - 2040

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 17

ER -