Activation of Dorsal Raphe Serotonin Neurons Underlies Waiting for Delayed Rewards

Miyazaki, Katsuhiko; Doya, Kenji

doi:10.1523/jneurosci.3714-10.2011

Cited by 208 publications

(192 citation statements)

References 48 publications

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“…We also found that the DRN 5-HT neuronal firing increased specifically while waiting for a delayed reward at reward sites and that the increase in 5-HT neural firing ceased before the rats gave up waiting for long delayed rewards (Miyazaki et al, 2011b). The present results revealed a causal relationship between 5-HT neural activity and waiting behavior for delayed rewards.…”

Section: Discussionsupporting

confidence: 72%

“…Recently, we showed that serotonin efflux in the DRN increases while rats perform a task that requires waiting for a delayed reward (Miyazaki et al, 2011a). We also found that DRN serotonergic neurons increase tonic firing while rats wait for delayed rewards and cease firing before rats give up waiting for long delayed rewards (Miyazaki et al, 2011b). These results demonstrated a correlation between dorsal raphe serotonin activation and waiting behavior for delayed rewards.…”

Section: Introductionsupporting

confidence: 54%

“…To examine this causality, we applied a 5-HT 1A receptor agonist locally in the DRN; this treatment is known to suppress 5-HT neural activity through autoreceptors. Systemic application of 5-HT 1A receptor agonists has been commonly used to suppress 5-HT neural activity in the DRN (Carli and Samanin, 2000;Casanovas et al, 2000;Waterhouse et al, 2004;Miyazaki et al, 2011b). However, systemic application can affect 5-HT 1A receptors in both the DRN and the projection sites, which can have different contributions to animal behaviors (Carli and Samanin, 2000;Assié et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Activation of Dorsal Raphe Serotonin Neurons Is Necessary for Waiting for Delayed Rewards

Miyazaki

Doya²

2012

Journal of Neuroscience

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The forebrain serotonergic system is a crucial component in the control of impulsive behaviors. We previously reported that the activity of serotonin neurons in the midbrain dorsal raphe nucleus increased when rats performed a task that required them to wait for delayed rewards. However, the causal relationship between serotonin neural activity and the tolerance for the delayed reward remained unclear. Here, we test whether the inhibition of serotonin neural activity by the local application of the 5-HT 1A receptor agonist 8-hydroxy-2-(din-propylamino) tetralin in the dorsal raphe nucleus impairs rats' tolerance for delayed rewards. Rats performed a sequential food-water navigation task that required them to visit food and water sites alternately via a tone site to get rewards at both sites after delays. During the short (2 s) delayed reward condition, the inhibition of serotonin neural activity did not significantly influence the numbers of reward choice errors (nosepoke at an incorrect reward site following a conditioned reinforcer tone), reward wait errors (failure to wait for the delayed rewards), or total trials (sum of reward choice errors, reward wait errors, and acquired rewards). By contrast, during the long (7-11 s) delayed reward condition, the number of wait errors significantly increased while the numbers of total trials and choice errors did not significantlychange.Theseresultsindicatethattheactivationofdorsalrapheserotoninneuronsisnecessaryforwaitingforlongdelayedrewards and suggest that elevated serotonin activity facilitates waiting behavior when there is the prospect of forthcoming rewards.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

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Activation of Dorsal Raphe Serotonin Neurons Is Necessary for Waiting for Delayed Rewards

Miyazaki

Doya²

2012

Journal of Neuroscience

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“…One remarkable observation from these studies is that neighboring 5-HT neurons have a high degree of diversity to respond to discrete stimuli, suggesting that 5-HT neurons are not a homogeneous population. 28,29 Our findings support this hypothesis, and confirm the existence of a subpopulation of serotonergic neurons that do not express the 5-HT1A receptor. It is difficult to speculate whether these cells correspond to any of the firing behaviors described for neurons recorded in vivo, or whether they could respond differently to external stimuli.…”

supporting

confidence: 83%

A Subpopulation of Serotonergic Neurons That Do Not Express the 5-HT1A Autoreceptor

Kiyasova

Bonnavion

Scotto-Lomassese

et al. 2012

ACS Chem. Neurosci.

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5-HT neurons are topographically organized in the hindbrain, and have been implicated in the etiology and treatment of psychiatric diseases such as depression and anxiety. Early studies suggested that the raphe 5-HT neurons were a homogeneous population showing similar electrical properties, and feedback inhibition mediated by 5-HT1A autoreceptors. We utilized histochemistry techniques in ePet1-eGFP and 5-HT1A-iCre/ R26R mice to show that a subpopulation of 5-HT neurons do not express the somatodendritic 5-HT1A autoreceptor mRNA. In addition, we performed patch-clamp recordings followed by singlecell PCR in ePet1-eGFP mice. From 134 recorded 5-HT neurons located in the dorsal, lateral, and median raphe, we found lack of 5-HT1A mRNA expression in 22 cells, evenly distributed across raphe subfields. We compared the cellular characteristics of these neuronal types and found no difference in passive membrane properties and general excitability. However, when injected with large depolarizing current, 5-HT1A-negative neurons fired more action potentials, suggesting a lack of autoinhibitory action of local 5-HT release. Our results support the hypothesis that the 5-HT system is composed of subpopulations of serotonergic neurons with different capacity for adaptation.T he 5-hydroxytryptamine (5-HT, serotonin) neurotransmitter system has been strongly implicated in the etiology and treatment of psychiatric diseases such as depression and anxiety. 1,2 5-HT neurons are topographically organized in the hindbrain where distinct groups of neurons receive and send synaptic inputs from/to specific brain regions, suggesting that the neuronal activity of subpopulation of 5-HT neurons is under discrete spatiotemporal control. 3 Given the occurrence of neurochemically diverse neurons in the raphe nuclei, early studies proposed a series of features or "landmarks", common to all 5-HT neurons, that would help in the identification of putative 5-HT cells. 4−6 These included the regular firing of broad action potentials (clocklike activity) followed by a large afterhyperpolarization potential, high input resistance, and suppression of firing by 5-hydroxytryptamine receptor 1A (5-HT1A) agonists. 4−6 However, this dogma is progressively being questioned. Recent studies found that the electrophysiological characteristics of chemically identified 5-HT neurons in the raphe are more diverse than originally thought. Using juxtacellular labeling techniques, it was found that, besides the population of slow-firing clocklike cells, in vivo discharge of 5-HT neurons also includes subpopulations of fastfiring and bursting neurons. 7,8 Moreover, in vitro patch-clamp studies conducted in brain slices demonstrated a high degree of variability in the passive and active membrane properties of 5-HT neurons. 9,10 Finally, anatomical and electrophysiological studies showed that 5-HT1A receptors are not only expressed in 5-HT neurons, but also in other neuronal classes in the raphe nuclei. 10−12 Together these evidence call to re-evaluate the defi...

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“…These results suggest that, at the stimulation patterns tested, DRN-Pet1 neurons represent a subpopulation of serotonergic neurons that promote reward behaviors in a glutamate and serotonin-dependent manner Luo et al 2015). One possibility is that increased reward learning is due to serotonin-mediated reduction in impulsivity, as previous studies found that serotonergic neurons in the DRN increase firing during a delay period before reward delivery and that optogenetic stimulation of serotonergic DRN neurons increases correct waiting behavior and performance during a delayed reward task (Miyazaki et al 2011(Miyazaki et al , 2014. When examining tonic firing within longer time scales, it was found that distinct populations of serotonergic neurons respond with higher firing rates during blocks of appetitive versus aversive trials, and vice versa (Cohen et al 2015).…”

Section: Dorsal Raphe Nuclei Projections To the Blamentioning

confidence: 83%

Input-specific contributions to valence processing in the amygdala

Correia

Goosens

2016

Learn. Mem.

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Reward and punishment are often thought of as opposing processes: rewards and the environmental cues that predict them elicit approach and consummatory behaviors, while punishments drive aversion and avoidance behaviors. This framework suggests that there may be segregated brain circuits for these valenced behaviors. The basolateral amygdala (BLA) is one brain region that contributes to both types of motivated behavior. Individual neurons in the BLA can favor positive over negative valence, or vice versa, but these neurons are intermingled, showing no anatomical segregation. The amygdala receives inputs from many brain areas and current theories posit that encoding of positive versus negative valence by BLA neurons is determined by the wiring of each neuron. Specifically, many projections from other brain areas that respond to positive and negative valence stimuli and predictive cues project strongly to the BLA and likely contribute to valence processing within the BLA. Here we review three of these areas, the basal forebrain, the dorsal raphe nucleus and the ventral tegmental area, and discuss how these may promote encoding of positive and negative valence within the BLA.The basic desire to seek reward and avoid punishment shapes virtually all of behavior, and the ability to discriminate between "good" and "bad" environmental cues is critical for guiding choices and maximizing survival. Thus, understanding the brain circuits that encode motivated behaviors is important because it contributes to our knowledge of how we learn, and it is also essential for understanding human disorders associated with abnormal processing of reward and danger (i.e., emotional disorders), such as anxiety, depression, addiction, and post-traumatic stress disorder (PTSD).The amygdala is one brain area implicated in motivated behaviors and the basolateral complex of the amygdala (BLA) receives information about diverse environmental stimuli from many brain regions. The BLA is thought to encode the association of predictive stimuli with both aversive and appetitive outcomes (Morrison and Salzman 2010;Barberini et al. 2012). Reward and punishment are reinforcers of opposite valence (positive versus negative), and these reinforcers typically lead to opposing behaviors (approach versus avoidance). Many theories have suggested that appetitive and aversive systems act in opponent fashion (Solomon and Corbit 1974;Daw et al. 2002). However, it is unclear how the BLA contributes to this. We do not yet understand the extent to which aversive and appetitive information is processed in parallel BLA circuits, or whether individual BLA neurons are involved in the regulation of both types of motivated behaviors.In this review, we propose several models by which functional segregation of valence can be achieved in the BLA. These models are based on studies describing how BLA neurons respond to reward and aversive stimuli. We then consider whether three major inputs, known to carry valenced information, support or conflict these models, and also discus...

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Activation of Dorsal Raphe Serotonin Neurons Underlies Waiting for Delayed Rewards

Cited by 208 publications

References 48 publications

Activation of Dorsal Raphe Serotonin Neurons Is Necessary for Waiting for Delayed Rewards

Activation of Dorsal Raphe Serotonin Neurons Is Necessary for Waiting for Delayed Rewards

A Subpopulation of Serotonergic Neurons That Do Not Express the 5-HT1A Autoreceptor

Input-specific contributions to valence processing in the amygdala

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