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Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action

In day-to-day life, we often choose between pursuing familiar behaviors that have been rewarded in the past or adjusting behaviors when new strategies might be more fruitful. The dorsomedial striatum (DMS) is indispensable for flexibly arbitrating between old and new behavioral strategies. The way i...

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Autores principales: Gourley, Shannon L., Srikanth, Kolluru D., Woon, Ellen P., Gil-Henn, Hava
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700592/
https://www.ncbi.nlm.nih.gov/pubmed/34943950
http://dx.doi.org/10.3390/cells10123442
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author Gourley, Shannon L.
Srikanth, Kolluru D.
Woon, Ellen P.
Gil-Henn, Hava
author_facet Gourley, Shannon L.
Srikanth, Kolluru D.
Woon, Ellen P.
Gil-Henn, Hava
author_sort Gourley, Shannon L.
collection PubMed
description In day-to-day life, we often choose between pursuing familiar behaviors that have been rewarded in the past or adjusting behaviors when new strategies might be more fruitful. The dorsomedial striatum (DMS) is indispensable for flexibly arbitrating between old and new behavioral strategies. The way in which DMS neurons host stable connections necessary for sustained flexibility is still being defined. An entry point to addressing this question may be the structural scaffolds on DMS neurons that house synaptic connections. We find that the non-receptor tyrosine kinase Proline-rich tyrosine kinase 2 (Pyk2) stabilizes both dendrites and spines on striatal medium spiny neurons, such that Pyk2 loss causes dendrite arbor and spine loss. Viral-mediated Pyk2 silencing in the DMS obstructs the ability of mice to arbitrate between rewarded and non-rewarded behaviors. Meanwhile, the overexpression of Pyk2 or the closely related focal adhesion kinase (FAK) enhances this ability. Finally, experiments using combinatorial viral vector strategies suggest that flexible, Pyk2-dependent action involves inputs from the medial prefrontal cortex (mPFC), but not the ventrolateral orbitofrontal cortex (OFC). Thus, Pyk2 stabilizes the striatal medium spiny neuron structure, likely providing substrates for inputs, and supports the capacity of mice to arbitrate between novel and familiar behaviors, including via interactions with the medial-prefrontal cortex.
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spelling pubmed-87005922021-12-24 Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action Gourley, Shannon L. Srikanth, Kolluru D. Woon, Ellen P. Gil-Henn, Hava Cells Article In day-to-day life, we often choose between pursuing familiar behaviors that have been rewarded in the past or adjusting behaviors when new strategies might be more fruitful. The dorsomedial striatum (DMS) is indispensable for flexibly arbitrating between old and new behavioral strategies. The way in which DMS neurons host stable connections necessary for sustained flexibility is still being defined. An entry point to addressing this question may be the structural scaffolds on DMS neurons that house synaptic connections. We find that the non-receptor tyrosine kinase Proline-rich tyrosine kinase 2 (Pyk2) stabilizes both dendrites and spines on striatal medium spiny neurons, such that Pyk2 loss causes dendrite arbor and spine loss. Viral-mediated Pyk2 silencing in the DMS obstructs the ability of mice to arbitrate between rewarded and non-rewarded behaviors. Meanwhile, the overexpression of Pyk2 or the closely related focal adhesion kinase (FAK) enhances this ability. Finally, experiments using combinatorial viral vector strategies suggest that flexible, Pyk2-dependent action involves inputs from the medial prefrontal cortex (mPFC), but not the ventrolateral orbitofrontal cortex (OFC). Thus, Pyk2 stabilizes the striatal medium spiny neuron structure, likely providing substrates for inputs, and supports the capacity of mice to arbitrate between novel and familiar behaviors, including via interactions with the medial-prefrontal cortex. MDPI 2021-12-07 /pmc/articles/PMC8700592/ /pubmed/34943950 http://dx.doi.org/10.3390/cells10123442 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gourley, Shannon L.
Srikanth, Kolluru D.
Woon, Ellen P.
Gil-Henn, Hava
Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title_full Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title_fullStr Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title_full_unstemmed Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title_short Pyk2 Stabilizes Striatal Medium Spiny Neuron Structure and Striatal-Dependent Action
title_sort pyk2 stabilizes striatal medium spiny neuron structure and striatal-dependent action
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700592/
https://www.ncbi.nlm.nih.gov/pubmed/34943950
http://dx.doi.org/10.3390/cells10123442
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