The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra
Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and substantia nigra, where they play a role in learning and control of motivated actions. However, the p...
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Public Library of Science
2018
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| Online Access: | http://hdl.handle.net/1721.1/116171 https://orcid.org/0000-0002-1981-1917 https://orcid.org/0000-0002-4326-7720 |
| _version_ | 1826198300387180544 |
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| author | Davis, Margaret I. Feng, Austin Y. Kupferschmidt, David A. Naydenov, Alipi Stella, Nephi Lovinger, David M. Crittenden, Jill R Graybiel, Ann M |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Davis, Margaret I. Feng, Austin Y. Kupferschmidt, David A. Naydenov, Alipi Stella, Nephi Lovinger, David M. Crittenden, Jill R Graybiel, Ann M |
| author_sort | Davis, Margaret I. |
| collection | MIT |
| description | Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs). CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR), which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets). Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals. These data suggest a role for CB1-Rs in caudal dorsolateral striosome collaterals and striosome-dendron bouquet projections to lateral substantia nigra, where they are anatomically poised to mediate presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons in response to endocannabinoids and cannabinomimetics. |
| first_indexed | 2024-09-23T11:02:42Z |
| format | Article |
| id | mit-1721.1/116171 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:02:42Z |
| publishDate | 2018 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/1161712019-05-17T09:23:09Z The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra Davis, Margaret I. Feng, Austin Y. Kupferschmidt, David A. Naydenov, Alipi Stella, Nephi Lovinger, David M. Crittenden, Jill R Graybiel, Ann M Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Crittenden, Jill R Graybiel, Ann M Presynaptic cannabinoid-1 receptors (CB1-R) bind endogenous and exogenous cannabinoids to modulate neurotransmitter release. CB1-Rs are expressed throughout the basal ganglia, including striatum and substantia nigra, where they play a role in learning and control of motivated actions. However, the pattern of CB1-R expression across different striatal compartments, microcircuits and efferent targets, and the contribution of different CB1-R-expressing neurons to this pattern, are unclear. We use a combination of conventional techniques and novel genetic models to evaluate CB1-R expression in striosome (patch) and matrix compartments of the striatum, and in nigral targets of striatal medium spiny projection neurons (MSNs). CB1-R protein and mRNA follow a descending dorsolateral-to-ventromedial intensity gradient in the caudal striatum, with elevated expression in striosomes relative to the surrounding matrix. The lateral predominance of striosome CB1-Rs contrasts with that of the classical striosomal marker, the mu opioid receptor (MOR), which is expressed most prominently in rostromedial striosomes. The dorsolateral-to-ventromedial CB1-R gradient is similar to Drd2 dopamine receptor immunoreactivity and opposite to Substance P. This topology of CB1-R expression is maintained downstream in the globus pallidus and substantia nigra. Dense CB1-R-expressing striatonigral fibers extend dorsally within the substantia nigra pars reticulata, and colocalize with bundles of ventrally extending, striosome-targeted, dendrites of dopamine-containing neurons in the substantia nigra pars compacta (striosome-dendron bouquets). Within striatum, CB1-Rs colocalize with fluorescently labeled MSN collaterals within the striosomes. Cre recombinase-mediated deletion of CB1-Rs from cortical projection neurons or MSNs, and MSN-selective reintroduction of CB1-Rs in knockout mice, demonstrate that the principal source of CB1-Rs in dorsolateral striosomes is local MSN collaterals. These data suggest a role for CB1-Rs in caudal dorsolateral striosome collaterals and striosome-dendron bouquet projections to lateral substantia nigra, where they are anatomically poised to mediate presynaptic disinhibition of both striosomal MSNs and midbrain dopamine neurons in response to endocannabinoids and cannabinomimetics. 2018-06-07T14:43:38Z 2018-06-07T14:43:38Z 2018-02 2018-05-04T18:15:35Z Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/116171 Davis, Margaret I. et al. “The Cannabinoid-1 Receptor Is Abundantly Expressed in Striatal Striosomes and Striosome-Dendron Bouquets of the Substantia Nigra.” Edited by Joohyung Lee. PLOS ONE 13, 2 (February 2018): e0191436 PUBLISHER_CC https://orcid.org/0000-0002-1981-1917 https://orcid.org/0000-0002-4326-7720 http://dx.doi.org/10.1371/journal.pone.0191436 PLOS ONE CC0 1.0 Universal (CC0 1.0) https://creativecommons.org/publicdomain/zero/1.0/ application/pdf Public Library of Science Public Library of Science |
| spellingShingle | Davis, Margaret I. Feng, Austin Y. Kupferschmidt, David A. Naydenov, Alipi Stella, Nephi Lovinger, David M. Crittenden, Jill R Graybiel, Ann M The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title | The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title_full | The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title_fullStr | The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title_full_unstemmed | The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title_short | The cannabinoid-1 receptor is abundantly expressed in striatal striosomes and striosome-dendron bouquets of the substantia nigra |
| title_sort | cannabinoid 1 receptor is abundantly expressed in striatal striosomes and striosome dendron bouquets of the substantia nigra |
| url | http://hdl.handle.net/1721.1/116171 https://orcid.org/0000-0002-1981-1917 https://orcid.org/0000-0002-4326-7720 |
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