Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release

Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosom...

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Autores principales:	J. A. Nadel, S. S. Pawelko, J. R. Scott, R. McLaughlin, M. Fox, M. Ghanem, R. van der Merwe, N. G. Hollon, E. S. Ramsson, C. D. Howard
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4e8acaad773d4e058966b14789886103
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spelling	oai:doaj.org-article:4e8acaad773d4e058966b147898861032021-12-02T19:16:18ZOptogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release10.1038/s41598-021-99350-52045-2322https://doaj.org/article/4e8acaad773d4e058966b147898861032021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99350-5https://doaj.org/toc/2045-2322Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.J. A. NadelS. S. PawelkoJ. R. ScottR. McLaughlinM. FoxM. GhanemR. van der MerweN. G. HollonE. S. RamssonC. D. HowardNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q J. A. Nadel S. S. Pawelko J. R. Scott R. McLaughlin M. Fox M. Ghanem R. van der Merwe N. G. Hollon E. S. Ramsson C. D. Howard Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
description	Abstract Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small ‘extinction burst’, further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.
format	article
author	J. A. Nadel S. S. Pawelko J. R. Scott R. McLaughlin M. Fox M. Ghanem R. van der Merwe N. G. Hollon E. S. Ramsson C. D. Howard
author_facet	J. A. Nadel S. S. Pawelko J. R. Scott R. McLaughlin M. Fox M. Ghanem R. van der Merwe N. G. Hollon E. S. Ramsson C. D. Howard
author_sort	J. A. Nadel
title	Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
title_short	Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
title_full	Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
title_fullStr	Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
title_full_unstemmed	Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
title_sort	optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4e8acaad773d4e058966b14789886103
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Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release

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