p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

Hanada, Yuuki; Kawahara, Yukie; Ohnishi, Yoshinori N.; Shuto, Takahide; Kuroiwa, Mahomi; Sotogaku, Naoki; Greengard, Paul; Sagi, Yotam; Nishi, Akinori

doi:10.1523/eneuro.0332-18.2018

Cited by 23 publications

(30 citation statements)

References 42 publications

(82 reference statements)

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“…The deletion of p11 from PV cells did not induce anhedonia or helplessness behaviors. This is in line with previous reports showing that deficits in reward and motivation-related behaviors are found in mice with constitutive deletion of p11 or in those with conditional deletion in the cholinergic neurons of the nucleus accumbens 11,35,36 . The idea that differences in mood-related behaviors are regulated by p11 in different cell types and brain regions is supported by the fact that the behavioral response to SSRIs is impaired in mice with deletion of p11 from hippocampal CCK, mossy cells and layer 5a cortical cells, but not cholinergic accumbal cells 16,32,35,37 .…”

Section: Multiple Roles For Dg Pv Cells In Mood-related Behaviorssupporting

confidence: 93%

Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression

Medrihan

Umschweif

Sinha

et al. 2019

Preprint

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Parvalbumin (PV)-expressing interneurons are important for cognitive and emotional behaviors.These neurons express high level of p11, a protein associated with depression and action of antidepressants. Here we show that either specific deletion of p11 (p11 cKO) or chemogenetic inhibition in dentate gyrus (DG) PV neurons leads to anxiety-like behavior and susceptibility to depression in mice. DG PV neurons from p11 cKO mice showed reduced level and function of Kv3.1, and consequentially reduced capacity of high-frequency firing and altered short-term plasticity at synapses on granule cells. Activation of Kv3.1 or overexpression of the channel attenuated the vulnerability to depressive behavior.

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Section: Multiple Roles For Dg Pv Cells In Mood-related Behaviorssupporting

confidence: 93%

Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression

Medrihan

Umschweif

Sinha

et al. 2019

Preprint

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“…A small receptor-binding protein p11 is a critical regulator of ChI activity within the NAc, as measured by the DA response to the mesolimbic DA reward stimulus pathway (Hanada et al, 2018 ; Liu et al, 2019 ). p11 is required for reward-mediated NAc ChI activation and the induction of acetylcholine (ACh) release, resulting in the enhancement of DA release (Hanada et al, 2018 ). Moreover, p11 in ChIs is shown to be a key regulator of depressive-like behavior.…”

Section: Possible Influencing Factors That Mediate the Comorbidity Ofmentioning

confidence: 99%

The Nucleus Accumbens: A Common Target in the Comorbidity of Depression and Addiction

Nan

2020

Front. Neural Circuits

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The comorbidity of depression and addiction has become a serious public health issue, and the relationship between these two disorders and their potential mechanisms has attracted extensive attention. Numerous studies have suggested that depression and addiction share common mechanisms and anatomical pathways. The nucleus accumbens (NAc) has long been considered a key brain region for regulating many behaviors, especially those related to depression and addiction. In this review article, we focus on the association between addiction and depression, highlighting the potential mediating role of the NAc in this comorbidity via the regulation of changes in the neural circuits and molecular signaling. To clarify the mechanisms underlying this association, we summarize evidence from overlapping reward neurocircuitry, the resemblance of cellular and molecular mechanisms, and common treatments. Understanding the interplay between these disorders should help guide clinical comorbidity prevention and the search for a new target for comorbidity treatment.

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“…For example, Rayport and colleagues have identified mNAcSh cholinergic interneurons as a preferential target of glutamate release from DA neurons, as glutamate co-release from DA neurons drives burst firing of mNAcSh cholinergic interneurons [15,114]. Cholinergic interneurons in the mNAcSh have also been implicated in reward processing and aversive learning, and they are activated by cocaine self-administration [115][116][117][118][119]. Together, these findings suggest glutamate release from DA neurons may mediate some actions of drugs of abuse by activating cholinergic interneurons in the mNAcSh.…”

Section: Future Directions and Conclusionmentioning

confidence: 99%

Roles of dopamine and glutamate co‐release in the nucleus accumbens in mediating the actions of drugs of abuse

et al. 2020

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Projections of ventral tegmental area dopamine (DA) neurons to the medial shell of the nucleus accumbens have been increasingly implicated as integral to the behavioral and physiological changes involved in the development of substance use disorders (SUDs). Recently, many of these nucleus accumbens-projecting DA neurons were found to also release the neurotransmitter glutamate. This glutamate co-release from DA neurons is critical in mediating the effect of drugs of abuse on addiction-related behaviors. Potential mechanisms underlying the role(s) of dopamine/glutamate co-release in contributing to SUDs are unclear. Nevertheless, an important clue may relate to glutamate's ability to potentiate loading of DA into synaptic vesicles within terminals in the nucleus accumbens in response to drug-induced elevations in neuronal activity, enabling a more robust release of DA after stimulation. Here, we summarize how drugs of abuse, particularly cocaine, opioids, and alcohol, alter DA release in the nucleus accumbens medial shell, examine the potential role of DA/glutamate co-release in mediating these effects, and discuss future directions for further investigating these mechanisms.

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p11 in Cholinergic Interneurons of the Nucleus Accumbens Is Essential for Dopamine Responses to Rewarding Stimuli

Abstract: Visual Abstract

Cited by 23 publications

References 42 publications

Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression

Reduced Kv3.1 Activity in Dentate Gyrus Parvalbumin Cells Induces Vulnerability to Depression

The Nucleus Accumbens: A Common Target in the Comorbidity of Depression and Addiction

Roles of dopamine and glutamate co‐release in the nucleus accumbens in mediating the actions of drugs of abuse

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