An emerging role for the lateral habenula in aggressive behavior

Flanigan, Meghan E.; Aleyasin, Hossein; Takahashi, Akiyoshi; Golden, Sam A.; Russo, Scott J.

doi:10.1016/j.pbb.2017.05.003

Cited by 52 publications

(39 citation statements)

References 122 publications

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“…We focused on the nucleus accumbens (NAc), which earlier research has implicated in aggression self-administration and CPP (Couppis and Kennedy, 2008;Golden et al, 2016;Aleyasin et al, 2018b). There has been a recent interest in the role of the mesolimbic dopaminergic circuit in controlling aggression reward (Flanigan et al, 2017;Aleyasin et al, 2018a;Yamaguchi and Lin, 2018), as dopaminergic projections from the ventral tegmental area (VTA) to the NAc modulate both aggression intensity (Yu et al, 2014) and NAc dopamine levels Miczek, 2000, 2007). Additionally, local dopamine receptor blockade decreases aggression-reinforced operant responding (Couppis and Kennedy, 2008).…”

Section: Introductionmentioning

confidence: 99%

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

et al. 2019

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We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate male mice and relapse to aggression seeking during abstinence. Here we studied the role of nucleus accumbens (NAc) dopamine receptor (Drd)1-and Drd2-expressing neurons in aggression self-administration and aggression seeking. We trained CD-1 mice to self-administer intruders (9 d, 12 trials/d) and tested them for aggression self-administration and aggression seeking on abstinence Day 1. We used immunohistochemistry and in situ hybridization to measure the neuronal activity marker Fos in the NAc, and cell-type-specific colocalization of Fos with Drd1-and Drd2-expressing neurons. To test the causal role of Drd1-and Drd2-expressing neurons, we validated a transgenic hybrid breeding strategy crossing inbred Drd1-Cre and Drd2-Cre transgenic mice with outbred CD-1 mice and used cell-type-specific Cre-DREADD (hM4Di) to inhibit NAc Drd1-and Drd2-expressing neuron activity. We found that aggression self-administration and aggression seeking induced higher Fos expression in NAc shell than in core, that Fos colocalized with Drd1 and Drd2 in both subregions, and that chemogenetic inhibition of Drd1-, but not Drd2-, expressing neurons decreased aggression self-administration and aggression seeking. Results indicate a cell-type-specific role of Drd1-expressing neurons that is critical for both aggression self-administration and aggression seeking. Our study also validates a simple breeding strategy between outbred CD-1 mice and inbred C57-based Cre lines that can be used to study cell-type and circuit mechanisms of aggression reward and relapse.Aggression is often comorbid with neuropsychiatric diseases, including drug addiction. One form, appetitive aggression, exhibits symptomatology that mimics that of drug addiction and is hypothesized to be due to dysregulation of addiction-related reward circuits. However, our mechanistic understanding of the circuitry modulating appetitive operant aggression is limited. Here we used a novel mouse model of aggression self-administration and relapse, in combination with immunohistochemistry, in situ hybridization, and chemogenetic manipulations to examine how cell types in the nucleus accumbens are recruited for, and control, operant aggression self-administration and aggression seeking on abstinence Day 1. We found that one population, dopamine receptor 1-expressing neurons, act as a critical modulator of operant aggression reward and aggression seeking.

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Section: Introductionmentioning

confidence: 99%

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

et al. 2019

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“…The epithalamus is part of the vertebrate dorsal diencephalic conduction system, involved in cognition, motivation and control of behavioural response (Concha & Wilson, 2001;Golden et al, 2016). Of particular interest is the habenular region, which is responsible for controlling neurotransmission from the forebrain and hypothalamus to the hindbrain and is arguably associated with the development of behavioral phenotypes (Andrew, 2006;Flanigan, Aleyasin, Takahashi, Golden & Russo, 2017). In zebrafish, the development of asymmetries in size and efferent innervation between the left and right habenula (Barth et al, 2005) and the directional location of the parapineal organ (Dadda et al, 2010) are linked to both the direction of sensory lateralisations and to behavioural responses towards imminent risk and novel settings.…”

Section: Discussionmentioning

confidence: 99%

Relationships between personality and lateralization of sensory inputs

et al. 2018

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In humans and other vertebrates, sensory information is sometimes lateralised towards one brain hemisphere that dominates the control of a task. Although sensory lateralisation may depend on the stimuli being processed, the degree or direction of lateralisation can differ according to behavioural phenotype. Accordingly, personality may play an important role in lateralisation, yet there is a lack of evidence regarding how laterlisations are utilised to process information and promote a personality-based response to a particular situation. Here we show that simultaneous stimulus processing and organisation of personality-based responses can be accomplished via differences in laterality between senses. We demonstrate this by examining novel-object inspection in the weakly-electric fish Gnathonemus petersii. Our findings reveal that electrosensing is lateralised in this species, but differently between personality phenotypes; bold fish lateralise towards the right and timid fish the left hemisphere. By contrast, visual laterality did not vary with personality; rather the left hemisphere was dominant across the population, as is common for fish when visually analysing unfamiliar objects. This evidence demonstrates differences in functional laterality between sensory systems and the role of personality in eliciting these differences. The species has a stronger input of electrical than visual signals in its brain, therefore, sensory representation in the brain might drive the laterality differences.

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“…These include GABAergic neurons from basal forebrain (BF), diagonal band, ventral pallidum, entopeduncular nucleus, and midbrain ventral tegmental neurons (Shabel et al, 2012;Stamatakis et al, 2013;Golden et al, 2016;Meye et al, 2016), and glutamatergic neurons from lateral hypothalamus, anterior cingulate, medial PFC, and entopeduncular nucleus (Li et al, 2011;Poller et al, 2013;Stamatakis et al, 2016). The diverse organization of LHb efferent and afferent projections allows control over dopaminergic and serotonergic tone, and therefore robust regulation of aggressive behavior (Flanigan et al, 2017).…”

Section: Neuroanatomical Mechanismsmentioning

confidence: 99%

Animal Models of (or for) Aggression Reward, Addiction, and Relapse: Behavior and Circuits

2019

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Inappropriate and pathological aggression plays a leading role in the suffering and death of millions of people, and further places an untenable strain on the caregivers and families of those afflicted. In some cases, such as addictive drugs, aggression can be highly rewarding (appetitive) and continually pursued despite short-and long-term negative consequences. Similarly, recidivism (relapse) rates for repeat violent offenders are as high as relapse rates for drug addicts. Appetitive aggression and relapse to aggression seeking can be modeled in mice studies using conditioned place preference and self-administration procedures followed by a period of abstinence and subsequent tests for relapse to aggression preference and aggression seeking. These procedures allow for the study of the mechanisms that control the appetitive versus the consummatory (attack) phases of aggressive behavior. In this review, we first discuss the behavioral procedures developed to probe appetitive aggression in mouse models, spanning from Pavlovian to operant tasks, and we also describe the recently proposed phenomenon of "aggression addiction." Next, we discuss the pharmacological and circuit mechanisms of aggression conditioned place preference and aggression self-administration, seeking, and relapse, highlighting mechanistic congruence and divergence between appetitive and consummatory phases of aggression. We conclude by discussing clinical implications of the studies reviewed.

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An emerging role for the lateral habenula in aggressive behavior

Cited by 52 publications

References 122 publications

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

Relationships between personality and lateralization of sensory inputs

Animal Models of (or for) Aggression Reward, Addiction, and Relapse: Behavior and Circuits

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