Activation of Dorsal Raphe Serotonergic Neurons Promotes Waiting but Is Not Reinforcing

Fonseca, Madalena S.; Murakami, Masayoshi; Mainen, Zachary F.

doi:10.1016/j.cub.2014.12.002

Cited by 185 publications

(223 citation statements)

References 44 publications

(82 reference statements)

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“…The second major conclusion arises from two optogenetic studies that demonstrate a significant effect of activating DRN 5-HT neurons on promoting reward waiting (Miyazaki et al 2014;Fonseca et al 2015). In both studies, mice were trained to perform a delayed reward task.…”

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

“…In both studies, mice were trained to perform a delayed reward task. Optogenetic stimulation of DRN 5-HT neurons increases animal's capacity of waiting for delayed reward delivery (Miyazaki et al 2014;Fonseca et al 2015). Furthermore, the patience-promoting effect does not rely on behavioral reinforcement.…”

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

“…Additional experiments are required to clarify why mouse behaviors are strongly reinforced by stimulation of Pet-1 neurons but not 5-HT neurons marked with SERT or Tph2 (Liu et al 2014;McDevitt et al 2014;Miyazaki et al 2014;Fonseca et al 2015). One possibility lies in the choice of mouse lines.…”

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

“…The discrepancy might be additionally produced by differences in optogenetic tools, labeling efficiency, stimulation parameters (intensity and duration), and behavioral tests (Table 1). For example, we used brief stimulation of DRN Pet-1 neurons (Liu et al 2014), whereas other studies used slightly longer and weaker stimulation of Tph2-expressing or SERT-expressing neurons (Miyazaki et al 2014;Fonseca et al 2015). Regardless the exact technical reasons, the optogenetic studies raise an important question on the exact contribution of glutamate and 5-HT to the reinforcement and reward waiting potentials of DRN neurons.…”

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

“…Regardless the exact technical reasons, the optogenetic studies raise an important question on the exact contribution of glutamate and 5-HT to the reinforcement and reward waiting potentials of DRN neurons. It has been proposed that the rewarding effect of DRN stimulation is mediated by the glutamate transmission from the DRN to the VTA (McDevitt et al 2014;Miyazaki et al 2014;Qi et al 2014;Ranade et al 2014;Fonseca et al 2015;McDannald 2015). However, several lines of evidences suggest that this interpretation might be overly simplified.…”

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

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Reward processing by the dorsal raphe nucleus: 5-HT and beyond

2015

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The dorsal raphe nucleus (DRN) represents one of the most sensitive reward sites in the brain. However, the exact relationship between DRN neuronal activity and reward signaling has been elusive. In this review, we will summarize anatomical, pharmacological, optogenetics, and electrophysiological studies on the functions and circuit mechanisms of DRN neurons in reward processing. The DRN is commonly associated with serotonin (5-hydroxytryptamine; 5-HT), but this nucleus also contains neurons of the neurotransmitter phenotypes of glutamate, GABA and dopamine. Pharmacological studies indicate that 5-HT might be involved in modulating reward-or punishment-related behaviors. Recent optogenetic stimulations demonstrate that transient activation of DRN neurons produces strong reinforcement signals that are carried out primarily by glutamate. Moreover, activation of DRN 5-HT neurons enhances reward waiting. Electrophysiological recordings reveal that the activity of DRN neurons exhibits diverse behavioral correlates in reward-related tasks. Studies so far thus demonstrate the strong power of DRN neurons in reward signaling and at the same time invite additional efforts to dissect the roles and mechanisms of different DRN neuron types in various processes of reward-related behaviors.

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Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

Section: Optogenetics Reveal Two Different Roles Of Drn Neurons In Rementioning

confidence: 99%

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Reward processing by the dorsal raphe nucleus: 5-HT and beyond

2015

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Aggression modulator: Understanding the multifaceted role of the dorsal raphe nucleus

Mitsui,

Takahashi

2024

BioEssays

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Aggressive behavior is instinctively driven behavior that helps animals to survive and reproduce and is closely related to multiple behavioral and physiological processes. The dorsal raphe nucleus (DRN) is an evolutionarily conserved midbrain structure that regulates aggressive behavior by integrating diverse brain inputs. The DRN consists predominantly of serotonergic (5‐HT:5‐hydroxytryptamine) neurons and decreased 5‐HT activity was classically thought to increase aggression. However, recent studies challenge this 5‐HT deficiency model, revealing a more complex role for the DRN 5‐HT system in aggression. Furthermore, emerging evidence has shown that non‐5‐HT populations in the DRN and specific neural circuits contribute to the escalation of aggressive behavior. This review argues that the DRN serves as a multifaceted modulator of aggression, acting not only via 5‐HT but also via other neurotransmitters and neural pathways, as well as different subsets of 5‐HT neurons. In addition, we discuss the contribution of DRN neurons in the behavioral and physiological aspects implicated in aggressive behavior, such as arousal, reward, and impulsivity, to further our understanding of DRN‐mediated aggression modulation.

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