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Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system

Prefrontal cortical influence over the mesolimbic system – including the nucleus accumbens (NAc) and the ventral tegmental area (VTA) – is implicated in various cognitive processes and behavioral malfunctions. The functional versatility of this system could be explained by an underlying anatomical c...

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Autores principales: Babiczky, Ákos, Matyas, Ferenc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444245/
https://www.ncbi.nlm.nih.gov/pubmed/36063145
http://dx.doi.org/10.7554/eLife.78813
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author Babiczky, Ákos
Matyas, Ferenc
author_facet Babiczky, Ákos
Matyas, Ferenc
author_sort Babiczky, Ákos
collection PubMed
description Prefrontal cortical influence over the mesolimbic system – including the nucleus accumbens (NAc) and the ventral tegmental area (VTA) – is implicated in various cognitive processes and behavioral malfunctions. The functional versatility of this system could be explained by an underlying anatomical complexity; however, the detailed characterization of the medial prefrontal cortical (mPFC) innervation of the NAc and VTA is still lacking. Therefore, combining classical retrograde and conditional viral tracing techniques with multiple fluorescent immunohistochemistry, we sought to deliver a precise, cell- and layer-specific anatomical description of the cortico-mesolimbic pathways in mice. We demonstrated that NAc- (mPFC(NAc)) and VTA-projecting mPFC (mPFC(VTA)) populations show different laminar distribution (layers 2/3–5a and 5b–6, respectively) and express different molecular markers. Specifically, calbindin and Ntsr1 are specific to mPFC(NAc) neurons, while mPFC(VTA) neurons express high levels of Ctip2 and FoxP2, indicating that these populations are mostly separated at the cellular level. We directly tested this with double retrograde tracing and Canine adenovirus type 2-mediated viral labeling and found that there is indeed minimal overlap between the two populations. Furthermore, whole-brain analysis revealed that the projection pattern of these populations is also different throughout the brain. Taken together, we demonstrated that the NAc and the VTA are innervated by two, mostly nonoverlapping mPFC populations with different laminar distribution and molecular profile. These results can contribute to the advancement in our understanding of mesocorticolimbic functions and its disorders in future studies.
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spelling pubmed-94442452022-09-06 Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system Babiczky, Ákos Matyas, Ferenc eLife Neuroscience Prefrontal cortical influence over the mesolimbic system – including the nucleus accumbens (NAc) and the ventral tegmental area (VTA) – is implicated in various cognitive processes and behavioral malfunctions. The functional versatility of this system could be explained by an underlying anatomical complexity; however, the detailed characterization of the medial prefrontal cortical (mPFC) innervation of the NAc and VTA is still lacking. Therefore, combining classical retrograde and conditional viral tracing techniques with multiple fluorescent immunohistochemistry, we sought to deliver a precise, cell- and layer-specific anatomical description of the cortico-mesolimbic pathways in mice. We demonstrated that NAc- (mPFC(NAc)) and VTA-projecting mPFC (mPFC(VTA)) populations show different laminar distribution (layers 2/3–5a and 5b–6, respectively) and express different molecular markers. Specifically, calbindin and Ntsr1 are specific to mPFC(NAc) neurons, while mPFC(VTA) neurons express high levels of Ctip2 and FoxP2, indicating that these populations are mostly separated at the cellular level. We directly tested this with double retrograde tracing and Canine adenovirus type 2-mediated viral labeling and found that there is indeed minimal overlap between the two populations. Furthermore, whole-brain analysis revealed that the projection pattern of these populations is also different throughout the brain. Taken together, we demonstrated that the NAc and the VTA are innervated by two, mostly nonoverlapping mPFC populations with different laminar distribution and molecular profile. These results can contribute to the advancement in our understanding of mesocorticolimbic functions and its disorders in future studies. eLife Sciences Publications, Ltd 2022-09-05 /pmc/articles/PMC9444245/ /pubmed/36063145 http://dx.doi.org/10.7554/eLife.78813 Text en © 2022, Babiczky and Matyas https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Babiczky, Ákos
Matyas, Ferenc
Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title_full Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title_fullStr Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title_full_unstemmed Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title_short Molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
title_sort molecular characteristics and laminar distribution of prefrontal neurons projecting to the mesolimbic system
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9444245/
https://www.ncbi.nlm.nih.gov/pubmed/36063145
http://dx.doi.org/10.7554/eLife.78813
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