Cholinergic neurons constitutively engage the ISR for dopamine modulation and skill learning in mice.
Science
; 372(6540)2021 04 23.
Article
em En
| MEDLINE
| ID: mdl-33888613
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Estresse Fisiológico
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Dopamina
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Neurônios Colinérgicos
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Interneurônios
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Aprendizagem
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article