Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..
The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning.
| Errataetall: |
CommentIn: Science. 2021 Apr 23;372(6540):345-346. - PMID 33888628 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:372 |
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| Enthalten in: |
Science (New York, N.Y.) - 372(2021), 6540 vom: 23. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Helseth, Ashley R [VerfasserIn] |
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| Links: |
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| Themen: |
DRD2 protein, mouse |
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| Anmerkungen: |
Date Completed 07.05.2021 Date Revised 15.03.2022 published: Print CommentIn: Science. 2021 Apr 23;372(6540):345-346. - PMID 33888628 Citation Status MEDLINE |
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| doi: |
10.1126/science.abe1931 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM324425791 |
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| 245 | 1 | 0 | |a Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice |
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| 500 | |a CommentIn: Science. 2021 Apr 23;372(6540):345-346. - PMID 33888628 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. | ||
| 520 | |a The integrated stress response (ISR) maintains proteostasis by modulating protein synthesis and is important in synaptic plasticity, learning, and memory. We developed a reporter, SPOTlight, for brainwide imaging of ISR state with cellular resolution. Unexpectedly, we found a class of neurons in mouse brain, striatal cholinergic interneurons (CINs), in which the ISR was activated at steady state. Genetic and pharmacological manipulations revealed that ISR signaling was necessary in CINs for normal type 2 dopamine receptor (D2R) modulation. Inhibiting the ISR inverted the sign of D2R modulation of CIN firing and evoked dopamine release and altered skill learning. Thus, a noncanonical, steady-state mode of ISR activation is found in CINs, revealing a neuromodulatory role for the ISR in learning | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
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| 650 | 7 | |a Receptors, Dopamine D2 |2 NLM | |
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| 700 | 1 | |a Oliver, Matthew L |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Brandon D |e verfasserin |4 aut | |
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| 700 | 1 | |a Rittiner, Joseph E |e verfasserin |4 aut | |
| 700 | 1 | |a Shipman, Miranda K |e verfasserin |4 aut | |
| 700 | 1 | |a King, Connor S |e verfasserin |4 aut | |
| 700 | 1 | |a Gradinaru, Viviana |e verfasserin |4 aut | |
| 700 | 1 | |a Gerfen, Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Costa-Mattioli, Mauro |e verfasserin |4 aut | |
| 700 | 1 | |a Calakos, Nicole |e verfasserin |4 aut | |
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