Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice

Flanigan, Meghan E.; Aleyasin, Hossein; Li, Long; Burnett, C. Joseph; Chan, Kenny L.; LeClair, Katherine B.; Lucas, Elizabeth K.; Matikainen‐Ankney, Bridget A.; Cuttoli, Romain Durand-de; Takahashi, Akiyoshi; Ménard, Caroline; Pfau, Madeline L.; Golden, Sam A.; Bouchard, Sylvain; Calipari, Erin S.; Nestler, Eric J.; DiLeone, Ralph J.; Yamanaka, Akihiro; Huntley, George W.; Clem, Roger L.; Russo, Scott J.

doi:10.1038/s41593-020-0617-7

Cited by 105 publications

(126 citation statements)

References 62 publications

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“…This functional heterogeneity within aminergic neurons provides flexibility in control of aggression according to social experience. Our findings parallel recent vertebrate studies reporting lateral habenula subpopulations that respond in opposite directions during aggressive encounters 36,37 .…”

Section: Nvy Marks Aggression-suppressing Neuronssupporting

confidence: 91%

A neurogenetic mechanism of experience-dependent suppression of aggression

Ishii

Cortese

Leng

et al. 2020

Preprint

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Aggression is an ethologically important social behavior1 but excessive aggression can be detrimental to animal fitness2,3. Social experiences among conspecific individuals reduce aggression in a wide range of animals4. However, the genetic and neural basis for the experience-dependent suppression of aggression remains largely unknown. Here we found that nervy (nvy), a Drosophila homolog of vertebrate myeloid translocation gene (MTG)5 involved in transcriptional regulation6–8, suppresses aggression via its action in a specific subset of neurons. Loss-of-function mutation of the nvy gene resulted in hyper-aggressiveness only in socially experienced flies, whereas overexpression of nvy suppressed spontaneous aggression in socially naïve flies. The loss-of-function nvy mutant exhibited persistent aggression under various contexts in which wild-type flies transition to escape or courtship behaviors. Knockdown of nvy in octopaminergic/tyraminergic (OA/TA) neurons increased aggression, phenocopying the nvy mutation. We found that a subpopulation of OA/TA cells specifically labeled by nvy is required for the social-experience-dependent suppression of aggression. Moreover, cell-type-specific transcriptomics on nvy-expressing OA/TA neurons revealed aggression-controlling genes that are likely downstream of nvy. Our results are the first to describe the presence of a specific neuronal subpopulation in the central brain that actively suppresses aggression in a social-experience-dependent manner, illuminating the underlying genetic mechanism.

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Section: Nvy Marks Aggression-suppressing Neuronssupporting

confidence: 91%

A neurogenetic mechanism of experience-dependent suppression of aggression

Ishii

Cortese

Leng

et al. 2020

Preprint

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“…Recently, Flanigan et al showed that the activation of GABAergic neurons in the LHb promoted male-male aggression and these GABAergic neurons were inhibitory within the LHb and dampened the activity of the LHb overall. 74 These data suggest that there are local circuits within the LHb. There is consensus that most of the neurons in the RMTg are GABAergic.…”

Section: Differences Between the Lhb And The Rmtgmentioning

confidence: 91%

The Rostromedial Tegmental Nucleus: Anatomical Studies and Roles in Sleep and Substance Addictions in Rats and Mice

Zhao¹,

Yan²,

Wang³

et al. 2020

NSS

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The rostromedial tegmental nucleus (RMTg), a brake of the dopamine system, is specifically activated by aversive stimuli, such as foot shock. It is principally composed of gamma-aminobutyric acid neurons. However, there is no exact location of the RMTg on the brain stereotaxic atlas. The RMTg can be defined by c-Fos staining elicited by psychostimulants, the position of retrograde-labeled neurons stained by injections into the ventral tegmental area (VTA), the terminal field formed by axons from the lateral habenula, and some molecular markers identified as specifically expressed in the RMTg such as FoxP1. The RMTg receives a broad range of inputs and produces diverse outputs, which indicates that the RMTg has multiple functions. First, the RMTg plays an essential role for non-rapid eye movement sleep. Additionally, the RMTg serves a vital role in response to addiction. Opiates increase the firing rates of dopaminergic neurons in the VTA by acting on μ-opioid receptors on RMTg neurons and their terminals inside the VTA. In this review, we summarize the recent research advances on the anatomical location of the RMTg in rats and mice, its projections, and its regulation of sleep–wake behavior and addiction.

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“…The anxiety level and locomotor function of the subjects were assessed by using the open-field test (Flanigan et al, 2020; Walsh et al, 2018). Briefly, a square open field (50 cm × 50 cm × 25 cm) was virtually subdivided into 16 even square.…”

Section: Methodsmentioning

confidence: 99%

Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability

Zhang

et al. 2020

Preprint

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Consolation is a common empathetic response in humans and some social animals, but the neural mechanisms underlying this behavior are not well characterized. Here, by using socially monogamous mandarin voles, we found that optogenetic or chemogenetic inhibition of 5-HTergic neurons in the dorsal raphe nuclei (DR) or optogenetic inhibition of 5-HT terminals in the anterior cingulate cortex (ACC) significantly decreased the allogrooming time in the consolation test and reduced sociability in the three-chamber test. Fiber photometry results showed that the release of 5-HT within the ACC and the activity of DR neurons were significantly increased when allogrooming and social approaching occurred. Finally, we found that the activation of 5-HT1A receptors in the ACC was sufficient to reverse consolation and sociability deficits induced by the chemogenetic inhibition of 5-HTergic neurons in the DR. Our study provided first direct evidence that DR→ACC 5-HTergic neural circuit is implicated in consolation-like behaviors and sociability in mandarin voles.

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Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice

Cited by 105 publications

References 62 publications

A neurogenetic mechanism of experience-dependent suppression of aggression

A neurogenetic mechanism of experience-dependent suppression of aggression

The Rostromedial Tegmental Nucleus: Anatomical Studies and Roles in Sleep and Substance Addictions in Rats and Mice

Dorsal raphe nucleus to anterior cingulate cortex 5-HTergic neural circuit modulates consolation and sociability

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