Corticosterone mediated functional and structural plasticity in corticotropin-releasing hormone neurons

Bittar, Thibault P.; Nair, Betina B.; Kim, Joon S.; Chandrasekera, Dhananjie; Sherrington, Aidan; Iremonger, Karl J.

doi:10.1016/j.neuropharm.2019.02.017

Cited by 20 publications

(20 citation statements)

References 56 publications

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“…4D). In control slices, we found that PVN-CRH neurons have relatively simple morphology, mostly with two to four primary dendrites (control, 2.4 ± 0.5, n = 8) in line with earlier studies in rats (Rho & Swanson, 1989) and mice (Bittar et al 2019). 21RRS did not change the number of primary dendrites (2.9 ± 1.0, n = 12; P = 0.15, Mann-Whitney test), total dendrite length (control, 398.4 ± 89.2 µm vs. 21RRS, 401.0 ± 141.1 µm, P = 0.84, unpaired t test) or the complexity of dendritic branching examined by Sholl analysis (Fig.…”

Section: Repeated Stress Increases Cell Sizesupporting

confidence: 91%

Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress

Matovic

Ichiyama

Ishii³

et al. 2020

The Journal of Physiology

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The hypothalamic-pituitary-adrenal (HPA) axis habituates to repeated stress exposure. r We studied hypothalamic corticotropin-releasing hormone (CRH) neurons that form the apex of the HPA axis in a mouse model of stress habituation using repeated restraint.r The intrinsic excitability of CRH neurons decreased after repeated stress in a time course that coincided with the development of HPA axis habituation.r This intrinsic excitability plasticity co-developed with an expansion of surface membrane area, which increased a passive electric load and dampened membrane depolarization in response to the influx of positive charge.r We report a novel structure-function relationship for intrinsic excitability plasticity as a neural correlate for HPA axis habituation.

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Section: Repeated Stress Increases Cell Sizesupporting

confidence: 91%

Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress

Matovic

Ichiyama

Ishii³

et al. 2020

The Journal of Physiology

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“…1a). This is consistent with blunted HPA activity, and is coherent with previous reports using similar CORT protocols over multiple weeks 9,21 .…”

Section: Mechanisms Of Cort Feedback Are Maintained After 7 Days Cortsupporting

confidence: 92%

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Rasiah

Rosenegger

Abant

et al. 2020

Preprint

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An increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRH PVN ), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRH PVN neurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable output in vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints.

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“…D2Rs are primarily expressed on dopamine neuronal dendrites and somata, but have also been localized to non-dopaminergic axon fibres in the VTA as well as astrocytes (Sesack et al, 1994). The restoration of synaptic transmission by D2R inhibition rules out possible synaptic scaling from CORT-exposure as has been observed in hypothalamic CRH neurons (Bittar et al, 2019). Taken together, chronic…”

Section: Vta Neuronal Excitability and Synaptic Transmission In Respomentioning

confidence: 85%

“…CORT may change neuronal excitability by directly targeting GR-or MR-expressing dopamine neurons to influence cellular activity or indirectly acting on upstream brain regions targeting VTA neurons. After chronic CORT treatment, hypothalamic GR-expressing CRH neurons exhibit reduced excitability (Bittar et al, 2019), whereas hippocampal neurons have enhanced excitatory postsynaptic receptor responses (Karst and Joels, 2005). Activation of these projections could drive VTA dopamine release.…”

Section: Vta Neuronal Excitability and Synaptic Transmission In Respomentioning

confidence: 99%

Corticosterone Attenuates Reward-Seeking Behavior and Increases Anxiety via D2 Receptor Signaling in Ventral Tegmental Area Dopamine Neurons

Peng

Liu

et al. 2020

J. Neurosci.

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Corticosteroids (CORT) have been widely used in anti-inflammatory medication. Chronic CORT treatment can cause mesocorticolimbic system dysfunctions, which are known to play a key role for the development of psychiatric disorders. The VTA is a critical site in the mesocorticolimbic pathway and is responsible for motivation and reward-seeking behaviors. However, the mechanism by which chronic CORT alters VTA dopamine neuronal activity is largely unknown. We treated periadolescent male mice with vehicle, 1 d, or 7 d CORT in the drinking water, examined behavioral impacts with light/dark box, elevated plus maze, operant chamber, and open field tests, measured the effects of CORT on VTA dopamine neuronal activity using patch-clamp electrophysiology and dopamine concentration using fast-scan cyclic voltammetry, and tested the effects of dopamine D2 receptor (D2R) blockade by intra-VTA infusion of a D2R antagonist. CORT treatment induced anxiety-like behavior as well as decreased food-seeking behaviors. We show that chronic CORT treatment decreased excitability and excitatory synaptic transmission onto VTA dopamine neurons. Furthermore, chronic CORT increased somatodendritic dopamine concentration. The D2R antagonist sulpiride restored decreased excitatory transmission and excitability of VTA dopamine neurons. Furthermore, sulpiride decreased anxiety-like behavior and rescued food-seeking behavior in mice with chronic CORT exposure. Together, 7 d CORT treatment induces anxiety-like behavior and impairs food-seeking in a mildly aversive environment. D2R signaling in the VTA might be a potential target to ameliorate chronic CORT-induced anxiety and reward-seeking deficits. SIGNIFICANCE STATEMENT With widespread anti-inflammatory effects throughout the body, corticosteroids (CORT) have been used in a variety of therapeutic conditions. However, long-term CORT treatment causes cognitive impairments and neuropsychiatric disorders. The impact of chronic CORT on the mesolimbic system has not been elucidated. Here, we demonstrate that 7 d CORT treatment increases anxiety-like behavior and attenuates food-seeking behavior in a mildly aversive environment. By elevating local dopamine concentration in the VTA, a region important for driving motivated behavior, CORT treatment suppresses excitability and synaptic transmission onto VTA dopamine neurons. Intriguingly, blockade of D2 receptor signaling in the VTA restores neuronal excitability and food-seeking and alleviates anxiety-like behaviors. Our findings provide a potential therapeutic target for CORT-induced reward deficits.

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Corticosterone mediated functional and structural plasticity in corticotropin-releasing hormone neurons

Cited by 20 publications

References 56 publications

Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress

Neuronal hypertrophy dampens neuronal intrinsic excitability and stress responsiveness during chronic stress

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Corticosterone Attenuates Reward-Seeking Behavior and Increases Anxiety via D2 Receptor Signaling in Ventral Tegmental Area Dopamine Neurons

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