Peptidergic and functional delineation of the Edinger-Westphal nucleus

Summary: Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower-acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether neurons that solely release peptides exist. Our fluores...

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Main Authors: Michael F. Priest, Sara N. Freda, Isabelle J. Rieth, Deanna Badong, Vasin Dumrongprechachan, Yevgenia Kozorovitskiy
Format: Article
Language:English
Published: Elsevier 2023-08-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723010033
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author Michael F. Priest
Sara N. Freda
Isabelle J. Rieth
Deanna Badong
Vasin Dumrongprechachan
Yevgenia Kozorovitskiy
author_facet Michael F. Priest
Sara N. Freda
Isabelle J. Rieth
Deanna Badong
Vasin Dumrongprechachan
Yevgenia Kozorovitskiy
author_sort Michael F. Priest
collection DOAJ
description Summary: Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower-acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether neurons that solely release peptides exist. Our fluorescence in situ hybridization, genetically targeted electron microscopy, and electrophysiological characterization suggest that most neurons of the non-cholinergic, centrally projecting Edinger-Westphal nucleus in mice are obligately peptidergic. We further show, using anterograde projection mapping, monosynaptic retrograde tracing, angled-tip fiber photometry, and chemogenetic modulation and genetically targeted ablation in conjunction with canonical assays for anxiety, that this peptidergic population activates in response to loss of motor control and promotes anxiety responses. Together, these findings elucidate an integrative, ethologically relevant role for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of peptidergic modulation of anxiety and provides a framework for future investigations of peptidergic systems.
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spelling doaj.art-84675cabcbab4daea75406df57c93dd82023-08-31T05:02:27ZengElsevierCell Reports2211-12472023-08-01428112992Peptidergic and functional delineation of the Edinger-Westphal nucleusMichael F. Priest0Sara N. Freda1Isabelle J. Rieth2Deanna Badong3Vasin Dumrongprechachan4Yevgenia Kozorovitskiy5Department of Neurobiology, Northwestern University, Evanston, IL 60208, USADepartment of Neurobiology, Northwestern University, Evanston, IL 60208, USADepartment of Neurobiology, Northwestern University, Evanston, IL 60208, USADepartment of Neurobiology, Northwestern University, Evanston, IL 60208, USADepartment of Neurobiology, Northwestern University, Evanston, IL 60208, USA; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USADepartment of Neurobiology, Northwestern University, Evanston, IL 60208, USA; Chemistry of Life Processes Institute, Northwestern University, Evanston, IL 60208, USA; Corresponding authorSummary: Many neuronal populations that release fast-acting excitatory and inhibitory neurotransmitters in the brain also contain slower-acting neuropeptides. These facultative peptidergic cell types are common, but it remains uncertain whether neurons that solely release peptides exist. Our fluorescence in situ hybridization, genetically targeted electron microscopy, and electrophysiological characterization suggest that most neurons of the non-cholinergic, centrally projecting Edinger-Westphal nucleus in mice are obligately peptidergic. We further show, using anterograde projection mapping, monosynaptic retrograde tracing, angled-tip fiber photometry, and chemogenetic modulation and genetically targeted ablation in conjunction with canonical assays for anxiety, that this peptidergic population activates in response to loss of motor control and promotes anxiety responses. Together, these findings elucidate an integrative, ethologically relevant role for the Edinger-Westphal nucleus and functionally align the nucleus with the periaqueductal gray, where it resides. This work advances our understanding of peptidergic modulation of anxiety and provides a framework for future investigations of peptidergic systems.http://www.sciencedirect.com/science/article/pii/S2211124723010033CP: Neuroscience
spellingShingle Michael F. Priest
Sara N. Freda
Isabelle J. Rieth
Deanna Badong
Vasin Dumrongprechachan
Yevgenia Kozorovitskiy
Peptidergic and functional delineation of the Edinger-Westphal nucleus
Cell Reports
CP: Neuroscience
title Peptidergic and functional delineation of the Edinger-Westphal nucleus
title_full Peptidergic and functional delineation of the Edinger-Westphal nucleus
title_fullStr Peptidergic and functional delineation of the Edinger-Westphal nucleus
title_full_unstemmed Peptidergic and functional delineation of the Edinger-Westphal nucleus
title_short Peptidergic and functional delineation of the Edinger-Westphal nucleus
title_sort peptidergic and functional delineation of the edinger westphal nucleus
topic CP: Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2211124723010033
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