Excitatory/inhibitory balance of serotonergic axon connectivity in the brain

Belmer, Arnauld

doi:10.29245/2572.942x/2016/9.1079

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…These findings add an important layer of complexity, i.e., the plasticity of neuron number, to stress-induced molecular changes. There is also ample electrophysiological evidence to suggest that serotonin exerts complex neuromodulation of the VTA in conjunction with glutamate and dopamine (Pessia et al, 1994;Gervais and Rouillard, 2000;Guiard et al, 2008;Liu et al, 2014;Belmer et al, 2016;Wang et al, 2019). Therefore, an increase in TPH2ϩ neurons in the DRv may lead to reduced reward function in the VTA.…”

Section: Discussionmentioning

confidence: 99%

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

et al. 2019

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Chronic stress induces anhedonia in susceptible but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward, and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in adult male rats using social defeat and intracranial self-stimulation, while changes in serotonergic phenotype were investigated using immunohistochemistry and in situ hybridization. Susceptible, but not resilient, rats displayed an increased number of neurons expressing the biosynthetic enzyme for serotonin, tryptophan-hydroxylase-2 (TPH2), in the ventral subnucleus of the dorsal raphe nucleus (DRv). Further, a decrease in the number of DRv glutamatergic (VGLUT3ϩ) neurons was observed in all stressed rats. This neurotransmitter plasticity is activity-dependent, as was revealed by chemogenetic manipulation of the central amygdala, a stress-sensitive nucleus that forms a major input to the DR. Activation of amygdalar corticotropin-releasing hormone (CRH)ϩ neurons abolished the increase in DRv TPH2ϩ neurons and ameliorated stress-induced anhedonia in susceptible rats. These findings show that activation of amygdalar CRHϩ neurons induces resilience, and suppresses the gain of serotonergic phenotype in the DRv that is characteristic of susceptible rats. This molecular signature of vulnerability to stress-induced anhedonia and the active nature of resilience could be targeted to develop new treatments for stress-related disorders like depression.

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Section: Discussionmentioning

confidence: 99%

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

et al. 2019

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“…This orchestrates intricate interplays amongst neuronal networks (e.g., glutamatergic, GABAergic, dopaminergic, serotonergic neurotransmission, etc.). Dysfunction in one of those neuronal networks could alter an E/I balance (Belmer et al, 2016 ; Hayashi-Takagi, 2017 ; Sonnenschein et al, 2020 ). Let us now focus on the units of neuronal networks, i.e., neuronal synapses.…”

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confidence: 99%

Editorial: New insights into schizophrenia-related neural and behavioral phenotypes

Sun¹,

Chen

2023

Front. Cell. Neurosci.

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Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

Prakash

Stark

Keisler

et al. 2019

Preprint

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critical feedback on the research and Dr.Byung Kook Lim for his valuable feedback and the use of his slide-scanning microscope. ABSTRACTChronic stress induces anhedonia in susceptible, but not resilient individuals, a phenomenon observed in humans as well as animal models, but the molecular mechanisms underlying susceptibility and resilience are not well understood. We hypothesized that the serotonergic system, which is implicated in stress, reward and antidepressant therapy, may play a role. We found that plasticity of the serotonergic system contributes to the differential vulnerability to stress displayed by susceptible and resilient animals. Stress-induced anhedonia was assessed in SIGNIFICANCE STATEMENTDepression and other mental disorders can be induced by chronic or traumatic stressors.However, some individuals are resilient and do not develop depression in response to chronic stress. A complete picture of the molecular differences between susceptible and resilient individuals is necessary to understand how plasticity of limbic circuits is associated with the pathophysiology of stress-related disorders. Using a rodent model, our study identifies a novel molecular marker of susceptibility to stress-induced anhedonia, a core symptom of depression, and a means to modulate it. These findings will guide further investigation into cellular and circuit mechanisms of resilience, and the development of new treatments for depression.

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Excitatory/inhibitory balance of serotonergic axon connectivity in the brain

Cited by 3 publications

References 40 publications

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

Serotonergic Plasticity in the Dorsal Raphe Nucleus Characterizes Susceptibility and Resilience to Anhedonia

Editorial: New insights into schizophrenia-related neural and behavioral phenotypes

Serotonergic plasticity in the dorsal raphe nucleus characterizes susceptibility and resilience to anhedonia

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