Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine
Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron micro...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-12-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/71981 |
| _version_ | 1811199468360433664 |
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| author | Gregg Wildenberg Anastasia Sorokina Jessica Koranda Alexis Monical Chad Heer Mark Sheffield Xiaoxi Zhuang Daniel McGehee Bobby Kasthuri |
| author_facet | Gregg Wildenberg Anastasia Sorokina Jessica Koranda Alexis Monical Chad Heer Mark Sheffield Xiaoxi Zhuang Daniel McGehee Bobby Kasthuri |
| author_sort | Gregg Wildenberg |
| collection | DOAJ |
| description | Dopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria. |
| first_indexed | 2024-04-12T01:49:49Z |
| format | Article |
| id | doaj.art-cc26fc1325a04c12a0acf1c299fd4096 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:49:49Z |
| publishDate | 2021-12-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj.art-cc26fc1325a04c12a0acf1c299fd40962022-12-22T03:52:59ZengeLife Sciences Publications LtdeLife2050-084X2021-12-011010.7554/eLife.71981Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaineGregg Wildenberg0https://orcid.org/0000-0003-2550-5497Anastasia Sorokina1Jessica Koranda2Alexis Monical3Chad Heer4Mark Sheffield5Xiaoxi Zhuang6Daniel McGehee7Bobby Kasthuri8https://orcid.org/0000-0003-3825-931XDepartment of Neurobiology, University of Chicago, Chicago, United States; Argonne National Laboratory, Lemont, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United States; Argonne National Laboratory, Lemont, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United StatesDepartment of Anesthesia & Critical Care, University of Chicago, Chicago, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United StatesDepartment of Anesthesia & Critical Care, University of Chicago, Chicago, United StatesDepartment of Neurobiology, University of Chicago, Chicago, United States; Argonne National Laboratory, Lemont, United StatesDopaminergic (DA) neurons exert profound influences on behavior including addiction. However, how DA axons communicate with target neurons and how those communications change with drug exposure remains poorly understood. We leverage cell type-specific labeling with large volume serial electron microscopy to detail DA connections in the nucleus accumbens (NAc) of the mouse (Mus musculus) before and after exposure to cocaine. We find that individual DA axons contain different varicosity types based on their vesicle contents. Spatially ordering along individual axons further suggests that varicosity types are non-randomly organized. DA axon varicosities rarely make specific synapses (<2%, 6/410), but instead are more likely to form spinule-like structures (15%, 61/410) with neighboring neurons. Days after a brief exposure to cocaine, DA axons were extensively branched relative to controls, formed blind-ended ‘bulbs’ filled with mitochondria, and were surrounded by elaborated glia. Finally, mitochondrial lengths increased by ~2.2 times relative to control only in DA axons and NAc spiny dendrites after cocaine exposure. We conclude that DA axonal transmission is unlikely to be mediated via classical synapses in the NAc and that the major locus of anatomical plasticity of DA circuits after exposure to cocaine are large-scale axonal re-arrangements with correlated changes in mitochondria.https://elifesciences.org/articles/71981connectomicsdopaminecocaineelectron microscopyanatomymouse |
| spellingShingle | Gregg Wildenberg Anastasia Sorokina Jessica Koranda Alexis Monical Chad Heer Mark Sheffield Xiaoxi Zhuang Daniel McGehee Bobby Kasthuri Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine eLife connectomics dopamine cocaine electron microscopy anatomy mouse |
| title | Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine |
| title_full | Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine |
| title_fullStr | Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine |
| title_full_unstemmed | Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine |
| title_short | Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine |
| title_sort | partial connectomes of labeled dopaminergic circuits reveal non synaptic communication and axonal remodeling after exposure to cocaine |
| topic | connectomics dopamine cocaine electron microscopy anatomy mouse |
| url | https://elifesciences.org/articles/71981 |
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