Protein kinase C mediates neuropeptide Y-induced reduction in inhibitory neurotransmission in the lateral habenula

Cheon, Myunghyun; Park, Ho-Yong; Chung, ChiHye

doi:10.1016/j.neuropharm.2020.108295

Cited by 4 publications

(4 citation statements)

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“…Neuropeptide Y (NPY) has recently been shown to modulate both excitatory and inhibitory synaptic transmission within the LHb (Cheon et al, 2019). Specifically, NPY receptor activation appears capable of bidirectionally modulating excitatory input in different groups of neurons, and has a net reduction of inhibitory input mediated by Y1 receptors (Cheon et al, 2019(Cheon et al, , 2020.…”

Section: Neuropeptide Ymentioning

confidence: 99%

Inhibition Within the Lateral Habenula—Implications for Affective Disorders

Webster

Lecca

Wozny

2021

Front. Behav. Neurosci.

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The lateral habenula (LHb) is a key brain region implicated in the pathology of major depressive disorder (MDD). Specifically, excitatory LHb neurons are known to be hyperactive in MDD, thus resulting in a greater excitatory output mainly to downstream inhibitory neurons in the rostromedial tegmental nucleus. This likely results in suppression of downstream dopaminergic ventral tegmental area neurons, therefore, resulting in an overall reduction in reward signalling. In line with this, increasing evidence implicates aberrant inhibitory signalling onto LHb neurons as a co-causative factor in MDD, likely as a result of disinhibition of excitatory neurons. Consistently, growing evidence now suggests that normalising inhibitory signalling within the LHb may be a potential therapeutic strategy for MDD. Despite these recent advances, however, the exact pharmacological and neural circuit mechanisms which control inhibitory signalling within the LHb are still incompletely understood. Thus, in this review article, we aim to provide an up-to-date summary of the current state of knowledge of the mechanisms by which inhibitory signalling is processed within the LHb, with a view of exploring how this may be targeted as a future therapy for MDD.

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Section: Neuropeptide Ymentioning

confidence: 99%

Inhibition Within the Lateral Habenula—Implications for Affective Disorders

Webster

Lecca

Wozny

2021

Front. Behav. Neurosci.

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“…In mice, Y1 and Y2 receptors, which are post-synaptic and pre-synaptic, respectively ( Shende and Desai, 2020 ), are expressed in the LHb ( Kopp et al, 2002 ; Stanić et al, 2006 ). In rats, exposure to NPY decreases the spontaneous firing rate of the LHb, leading to hypoactivation of the LHb, which is modulated by reduction of GABAergic transmission via the Y1 pathway ( Cheon et al, 2019 , 2020 ). Although a possible involvement of the habenula NPY-Y1 signaling in sexual and social behavior is not well known, NPY has been implicated in stress-related responses such as anxiety and depression ( Shende and Desai, 2020 ), which are closely associated with LHb dysfunction ( Hikosaka, 2010 ; Browne et al, 2018 ).…”

Section: Regulators Of Reproductive and Social Behaviors On The Habenulamentioning

confidence: 99%

“…In male mice, the AVP-V1aR signaling in the LHb has recently been implicated in the regulation of male-typical social communication including ultrasonic vocalization, but not other social functions such as aggression ( Rigney et al, 2020 ). On the other hand, AVP fibers in the medial division of the LHb (LHbM) derived from the PVN evoke GABA-mediated inhibition in the LHbM, which promotes escape behavior during stress coping ( Zhang et al, 2016 ), similar to the role of NPY on GABAergic LHb neurons ( Cheon et al, 2019 , 2020 ) (see above).…”

Section: Regulators Of Reproductive and Social Behaviors On The Habenulamentioning

confidence: 99%

Role of Habenula in Social and Reproductive Behaviors in Fish: Comparison With Mammals

Ogawa

Parhar

2022

Front. Behav. Neurosci.

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Social behaviors such as mating, parenting, fighting, and avoiding are essential functions as a communication tool in social animals, and are critical for the survival of individuals and species. Social behaviors are controlled by a complex circuitry that comprises several key social brain regions, which is called the social behavior network (SBN). The SBN further integrates social information with external and internal factors to select appropriate behavioral responses to social circumstances, called social decision-making. The social decision-making network (SDMN) and SBN are structurally, neurochemically and functionally conserved in vertebrates. The social decision-making process is also closely influenced by emotional assessment. The habenula has recently been recognized as a crucial center for emotion-associated adaptation behaviors. Here we review the potential role of the habenula in social function with a special emphasis on fish studies. Further, based on evolutional, molecular, morphological, and behavioral perspectives, we discuss the crucial role of the habenula in the vertebrate SDMN.

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“…It is the most prevalent and extensively distributed neuropeptide in the mammalian brain and plays an essential role in depression and stress ( 174 , 175 ). Activation of neuropeptide Y1 receptors leads to inhibition of excitatory neurotransmission in the vast majority of LHb neurons via the phospholipase C/protein kinase C-dependent pathway, while potentiation occurs in a small population of neurons ( 176 , 177 ). Despite this overall inhibitory activity, whether NPY in the LHb can suppress hyperactive LHb to improve depressive symptoms remains to be investigated.…”

Section: Molecular Mechanisms Of Lateral Habenula Activity Regulation...mentioning

confidence: 99%

Multi-level variations of lateral habenula in depression: A comprehensive review of current evidence

Zhang

Cui

et al. 2022

Front. Psychiatry

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Despite extensive research in recent decades, knowledge of the pathophysiology of depression in neural circuits remains limited. Recently, the lateral habenula (LHb) has been extensively reported to undergo a series of adaptive changes at multiple levels during the depression state. As a crucial relay in brain networks associated with emotion regulation, LHb receives excitatory or inhibitory projections from upstream brain regions related to stress and cognition and interacts with brain regions involved in emotion regulation. A series of pathological alterations induced by aberrant inputs cause abnormal function of the LHb, resulting in dysregulation of mood and motivation, which present with depressive-like phenotypes in rodents. Herein, we systematically combed advances from rodents, summarized changes in the LHb and related neural circuits in depression, and attempted to analyze the intrinsic logical relationship among these pathological alterations. We expect that this summary will greatly enhance our understanding of the pathological processes of depression. This is advantageous for fostering the understanding and screening of potential antidepressant targets against LHb.

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Protein kinase C mediates neuropeptide Y-induced reduction in inhibitory neurotransmission in the lateral habenula

Cited by 4 publications

References 53 publications

Inhibition Within the Lateral Habenula—Implications for Affective Disorders

Inhibition Within the Lateral Habenula—Implications for Affective Disorders

Role of Habenula in Social and Reproductive Behaviors in Fish: Comparison With Mammals

Multi-level variations of lateral habenula in depression: A comprehensive review of current evidence

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