Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions

Escaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters neuronal activity and neuromodulatory signaling in distributed networks, modifying behavior. Here, we describe changes in dopaminergic neuron activity and signa...

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Autores principales:	Mingzheng Wu, Samuel Minkowicz, Vasin Dumrongprechachan, Pauline Hamilton, Lei Xiao, Yevgenia Kozorovitskiy
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	dopamine aversive learning ketamine mPFC VTA Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/09407d483e4f4aacbb9ca3606361d869
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spelling	oai:doaj.org-article:09407d483e4f4aacbb9ca3606361d8692021-11-25T14:36:31ZAttenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions10.7554/eLife.640412050-084Xe64041https://doaj.org/article/09407d483e4f4aacbb9ca3606361d8692021-04-01T00:00:00Zhttps://elifesciences.org/articles/64041https://doaj.org/toc/2050-084XEscaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters neuronal activity and neuromodulatory signaling in distributed networks, modifying behavior. Here, we describe changes in dopaminergic neuron activity and signaling following aversive learning in a learned helplessness paradigm in mice. A single dose of ketamine suffices to restore escape behavior after aversive learning. Dopaminergic neuron activity in the ventral tegmental area (VTA) systematically varies across learning, correlating with future sensitivity to ketamine treatment. Ketamine’s effects are blocked by chemogenetic inhibition of dopamine signaling. Rather than directly altering the activity of dopaminergic neurons, ketamine appears to rescue dopamine dynamics through actions in the medial prefrontal cortex (mPFC). Chemogenetic activation of Drd1 receptor positive mPFC neurons mimics ketamine’s effects on behavior. Together, our data link neuromodulatory dynamics in mPFC-VTA circuits, aversive learning, and the effects of ketamine.Mingzheng WuSamuel MinkowiczVasin DumrongprechachanPauline HamiltonLei XiaoYevgenia KozorovitskiyeLife Sciences Publications Ltdarticledopamineaversive learningketaminemPFCVTAMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	dopamine aversive learning ketamine mPFC VTA Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	dopamine aversive learning ketamine mPFC VTA Medicine R Science Q Biology (General) QH301-705.5 Mingzheng Wu Samuel Minkowicz Vasin Dumrongprechachan Pauline Hamilton Lei Xiao Yevgenia Kozorovitskiy Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
description	Escaping aversive stimuli is essential for complex organisms, but prolonged exposure to stress leads to maladaptive learning. Stress alters neuronal activity and neuromodulatory signaling in distributed networks, modifying behavior. Here, we describe changes in dopaminergic neuron activity and signaling following aversive learning in a learned helplessness paradigm in mice. A single dose of ketamine suffices to restore escape behavior after aversive learning. Dopaminergic neuron activity in the ventral tegmental area (VTA) systematically varies across learning, correlating with future sensitivity to ketamine treatment. Ketamine’s effects are blocked by chemogenetic inhibition of dopamine signaling. Rather than directly altering the activity of dopaminergic neurons, ketamine appears to rescue dopamine dynamics through actions in the medial prefrontal cortex (mPFC). Chemogenetic activation of Drd1 receptor positive mPFC neurons mimics ketamine’s effects on behavior. Together, our data link neuromodulatory dynamics in mPFC-VTA circuits, aversive learning, and the effects of ketamine.
format	article
author	Mingzheng Wu Samuel Minkowicz Vasin Dumrongprechachan Pauline Hamilton Lei Xiao Yevgenia Kozorovitskiy
author_facet	Mingzheng Wu Samuel Minkowicz Vasin Dumrongprechachan Pauline Hamilton Lei Xiao Yevgenia Kozorovitskiy
author_sort	Mingzheng Wu
title	Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
title_short	Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
title_full	Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
title_fullStr	Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
title_full_unstemmed	Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
title_sort	attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/09407d483e4f4aacbb9ca3606361d869
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Attenuated dopamine signaling after aversive learning is restored by ketamine to rescue escape actions

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