Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line

Abstract A recently developed Phox2a::Cre mouse line has been shown to capture anterolateral system (ALS) projection neurons. Here, we used this line to test whether Phox2a-positive cells represent a distinct subpopulation among lamina I ALS neurons. We show that virtually all lamina I Phox2a cells...

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Autores principales:	Wafa A. A. Alsulaiman, Raphaelle Quillet, Andrew M. Bell, Allen C. Dickie, Erika Polgár, Kieran A. Boyle, Masahiko Watanabe, R. Brian Roome, Artur Kania, Andrew J. Todd, Maria Gutierrez-Mecinas
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/45445ef9894d49f187740e8e7d79332d
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spelling	oai:doaj.org-article:45445ef9894d49f187740e8e7d79332d2021-12-02T17:19:14ZCharacterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line10.1038/s41598-021-97105-w2045-2322https://doaj.org/article/45445ef9894d49f187740e8e7d79332d2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97105-whttps://doaj.org/toc/2045-2322Abstract A recently developed Phox2a::Cre mouse line has been shown to capture anterolateral system (ALS) projection neurons. Here, we used this line to test whether Phox2a-positive cells represent a distinct subpopulation among lamina I ALS neurons. We show that virtually all lamina I Phox2a cells can be retrogradely labelled from injections targeted on the lateral parabrachial area (LPb), and that most of those in the cervical cord also belong to the spinothalamic tract. Phox2a cells accounted for ~ 50–60% of the lamina I cells retrogradely labelled from LPb or thalamus. Phox2a was preferentially associated with smaller ALS neurons, and with those showing relatively weak neurokinin 1 receptor expression. The Phox2a cells were also less likely to project to the ipsilateral LPb. Although most Phox2a cells phosphorylated extracellular signal-regulated kinases following noxious heat stimulation, ~ 20% did not, and these were significantly smaller than the activated cells. This suggests that those ALS neurons that respond selectively to skin cooling, which have small cell bodies, may be included among the Phox2a population. Previous studies have defined neurochemical populations among the ALS cells, based on expression of Tac1 or Gpr83. However, we found that the proportions of Phox2a cells that expressed these genes were similar to the proportions reported for all lamina I ALS neurons, suggesting that Phox2a is not differentially expressed among cells belonging to these populations. Finally, we used a mouse line that resulted in membrane labelling of the Phox2a cells and showed that they all possess dendritic spines, although at a relatively low density. However, the distribution of the postsynaptic protein Homer revealed that dendritic spines accounted for a minority of the excitatory synapses on these cells. Our results confirm that Phox2a-positive cells in lamina I are ALS neurons, but show that the Phox2a::Cre line preferentially captures specific types of ALS cells.Wafa A. A. AlsulaimanRaphaelle QuilletAndrew M. BellAllen C. DickieErika PolgárKieran A. BoyleMasahiko WatanabeR. Brian RoomeArtur KaniaAndrew J. ToddMaria Gutierrez-MecinasNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wafa A. A. Alsulaiman Raphaelle Quillet Andrew M. Bell Allen C. Dickie Erika Polgár Kieran A. Boyle Masahiko Watanabe R. Brian Roome Artur Kania Andrew J. Todd Maria Gutierrez-Mecinas Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
description	Abstract A recently developed Phox2a::Cre mouse line has been shown to capture anterolateral system (ALS) projection neurons. Here, we used this line to test whether Phox2a-positive cells represent a distinct subpopulation among lamina I ALS neurons. We show that virtually all lamina I Phox2a cells can be retrogradely labelled from injections targeted on the lateral parabrachial area (LPb), and that most of those in the cervical cord also belong to the spinothalamic tract. Phox2a cells accounted for ~ 50–60% of the lamina I cells retrogradely labelled from LPb or thalamus. Phox2a was preferentially associated with smaller ALS neurons, and with those showing relatively weak neurokinin 1 receptor expression. The Phox2a cells were also less likely to project to the ipsilateral LPb. Although most Phox2a cells phosphorylated extracellular signal-regulated kinases following noxious heat stimulation, ~ 20% did not, and these were significantly smaller than the activated cells. This suggests that those ALS neurons that respond selectively to skin cooling, which have small cell bodies, may be included among the Phox2a population. Previous studies have defined neurochemical populations among the ALS cells, based on expression of Tac1 or Gpr83. However, we found that the proportions of Phox2a cells that expressed these genes were similar to the proportions reported for all lamina I ALS neurons, suggesting that Phox2a is not differentially expressed among cells belonging to these populations. Finally, we used a mouse line that resulted in membrane labelling of the Phox2a cells and showed that they all possess dendritic spines, although at a relatively low density. However, the distribution of the postsynaptic protein Homer revealed that dendritic spines accounted for a minority of the excitatory synapses on these cells. Our results confirm that Phox2a-positive cells in lamina I are ALS neurons, but show that the Phox2a::Cre line preferentially captures specific types of ALS cells.
format	article
author	Wafa A. A. Alsulaiman Raphaelle Quillet Andrew M. Bell Allen C. Dickie Erika Polgár Kieran A. Boyle Masahiko Watanabe R. Brian Roome Artur Kania Andrew J. Todd Maria Gutierrez-Mecinas
author_facet	Wafa A. A. Alsulaiman Raphaelle Quillet Andrew M. Bell Allen C. Dickie Erika Polgár Kieran A. Boyle Masahiko Watanabe R. Brian Roome Artur Kania Andrew J. Todd Maria Gutierrez-Mecinas
author_sort	Wafa A. A. Alsulaiman
title	Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
title_short	Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
title_full	Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
title_fullStr	Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
title_full_unstemmed	Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line
title_sort	characterisation of lamina i anterolateral system neurons that express cre in a phox2a-cre mouse line
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/45445ef9894d49f187740e8e7d79332d
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Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line

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