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Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra
The “habenulopeduncular system” consists of the medial habenula (MHb) and its principal target of innervation, the interpeduncular nucleus (IP). Neurons in the ventral MHb (MHbV) express acetylcholine along with glutamate, and both the MHb and IP are rich in nicotinic acetylcholine receptors. Much o...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Society for Neuroscience
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223495/ https://www.ncbi.nlm.nih.gov/pubmed/34088738 http://dx.doi.org/10.1523/ENEURO.0127-21.2021 |
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author | Nasirova, Nailyam Quina, Lely A. Novik, Shoshana Turner, Eric E. |
author_facet | Nasirova, Nailyam Quina, Lely A. Novik, Shoshana Turner, Eric E. |
author_sort | Nasirova, Nailyam |
collection | PubMed |
description | The “habenulopeduncular system” consists of the medial habenula (MHb) and its principal target of innervation, the interpeduncular nucleus (IP). Neurons in the ventral MHb (MHbV) express acetylcholine along with glutamate, and both the MHb and IP are rich in nicotinic acetylcholine receptors. Much of the work on this system has focused on nicotinic mechanisms and their clinical implications for nicotine use, particularly because the IP expresses the α5 nicotinic receptor subunit, encoded by the CHRNA5 gene, which is genetically linked to smoking risk. A working model has emerged in which nicotine use may be determined by the balance of reinforcement mediated in part by nicotine effects on dopamine reward pathways, and an aversive “brake” on nicotine consumption encoded in the MHb-IP pathway. However, recent work has proposed that the IP also receives direct dopaminergic input from the ventral tegmental area (VTA). If correct, this would significantly impact the prevailing model of IP function. Here, we have used Chrna5(Cre) mice to perform rabies virus-mediated retrograde tracing of global inputs to the IP. We have also used Cre-dependent adeno-associated virus (AAV) anterograde tracing using Slc6a3(Cre) (DAT(Cre)) mice to map VTA dopaminergic efferents, and we have examined tract-tracing data using other transgenic models for dopaminergic neurons available in a public database. Consistent with the existing literature using non-genetic tracing methods, none of these experiments show a significant anatomic connection from the VTA or substantia nigra (SN) to the IP, and thus do not support a model of direct dopaminergic input to the habenulopeduncular system. |
format | Online Article Text |
id | pubmed-8223495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Society for Neuroscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-82234952021-06-24 Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra Nasirova, Nailyam Quina, Lely A. Novik, Shoshana Turner, Eric E. eNeuro Research Article: New Research The “habenulopeduncular system” consists of the medial habenula (MHb) and its principal target of innervation, the interpeduncular nucleus (IP). Neurons in the ventral MHb (MHbV) express acetylcholine along with glutamate, and both the MHb and IP are rich in nicotinic acetylcholine receptors. Much of the work on this system has focused on nicotinic mechanisms and their clinical implications for nicotine use, particularly because the IP expresses the α5 nicotinic receptor subunit, encoded by the CHRNA5 gene, which is genetically linked to smoking risk. A working model has emerged in which nicotine use may be determined by the balance of reinforcement mediated in part by nicotine effects on dopamine reward pathways, and an aversive “brake” on nicotine consumption encoded in the MHb-IP pathway. However, recent work has proposed that the IP also receives direct dopaminergic input from the ventral tegmental area (VTA). If correct, this would significantly impact the prevailing model of IP function. Here, we have used Chrna5(Cre) mice to perform rabies virus-mediated retrograde tracing of global inputs to the IP. We have also used Cre-dependent adeno-associated virus (AAV) anterograde tracing using Slc6a3(Cre) (DAT(Cre)) mice to map VTA dopaminergic efferents, and we have examined tract-tracing data using other transgenic models for dopaminergic neurons available in a public database. Consistent with the existing literature using non-genetic tracing methods, none of these experiments show a significant anatomic connection from the VTA or substantia nigra (SN) to the IP, and thus do not support a model of direct dopaminergic input to the habenulopeduncular system. Society for Neuroscience 2021-06-18 /pmc/articles/PMC8223495/ /pubmed/34088738 http://dx.doi.org/10.1523/ENEURO.0127-21.2021 Text en Copyright © 2021 Nasirova et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article: New Research Nasirova, Nailyam Quina, Lely A. Novik, Shoshana Turner, Eric E. Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title | Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title_full | Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title_fullStr | Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title_full_unstemmed | Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title_short | Genetically Targeted Connectivity Tracing Excludes Dopaminergic Inputs to the Interpeduncular Nucleus from the Ventral Tegmentum and Substantia Nigra |
title_sort | genetically targeted connectivity tracing excludes dopaminergic inputs to the interpeduncular nucleus from the ventral tegmentum and substantia nigra |
topic | Research Article: New Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223495/ https://www.ncbi.nlm.nih.gov/pubmed/34088738 http://dx.doi.org/10.1523/ENEURO.0127-21.2021 |
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