Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum

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Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum. / Romero-Leguizamón, Cesar R; Kohlmeier, Kristi A.

In: European Neuropsychopharmacology, Vol. 38, 2020, p. 86-97.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Romero-Leguizamón, CR & Kohlmeier, KA 2020, 'Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum', European Neuropsychopharmacology, vol. 38, pp. 86-97. https://doi.org/10.1016/j.euroneuro.2020.07.008

APA

Romero-Leguizamón, C. R., & Kohlmeier, K. A. (2020). Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum. European Neuropsychopharmacology, 38, 86-97. https://doi.org/10.1016/j.euroneuro.2020.07.008

Vancouver

Romero-Leguizamón CR, Kohlmeier KA. Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum. European Neuropsychopharmacology. 2020;38:86-97. https://doi.org/10.1016/j.euroneuro.2020.07.008

Author

Romero-Leguizamón, Cesar R ; Kohlmeier, Kristi A. / Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum. In: European Neuropsychopharmacology. 2020 ; Vol. 38. pp. 86-97.

Bibtex

@article{3f0ec737ebd746f6b9350f3b3b022fa4,
title = "Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum",
abstract = "Stress is a physiological response that promotes maintenance of balance against harmful stimuli. Unfortunately, chronic activation of stress systems facilitates the development of psychiatric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and substance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin-releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically-identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state.",
author = "Romero-Leguizam{\'o}n, {Cesar R} and Kohlmeier, {Kristi A}",
note = "Copyright {\textcopyright} 2020. Published by Elsevier B.V.",
year = "2020",
doi = "10.1016/j.euroneuro.2020.07.008",
language = "English",
volume = "38",
pages = "86--97",
journal = "European Neuropsychopharmacology",
issn = "0924-977X",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Stress-related endogenous neuropeptides induce neuronal excitation in the Laterodorsal Tegmentum

AU - Romero-Leguizamón, Cesar R

AU - Kohlmeier, Kristi A

N1 - Copyright © 2020. Published by Elsevier B.V.

PY - 2020

Y1 - 2020

N2 - Stress is a physiological response that promotes maintenance of balance against harmful stimuli. Unfortunately, chronic activation of stress systems facilitates the development of psychiatric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and substance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin-releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically-identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state.

AB - Stress is a physiological response that promotes maintenance of balance against harmful stimuli. Unfortunately, chronic activation of stress systems facilitates the development of psychiatric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and substance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin-releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically-identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state.

U2 - 10.1016/j.euroneuro.2020.07.008

DO - 10.1016/j.euroneuro.2020.07.008

M3 - Journal article

C2 - 32768153

VL - 38

SP - 86

EP - 97

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

SN - 0924-977X

ER -

ID: 247209817