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

Alsulaiman, W. A.A. et al. (2021) Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line. Scientific Reports, 11, 17912. (doi: 10.1038/s41598-021-97105-w) (PMID:34504158) (PMCID:PMC8429737)

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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.

Item Type:Articles
Additional Information:Financial support from the Wellcome Trust (grants 102645/Z/13/Z and 219433/Z/19/Z) and the Medical Research Council (grant MR/S002987/1) is gratefully acknowledged.
Glasgow Author(s) Enlighten ID:Boyle, Dr Kieran and Bell, Mr Andrew and Beresford-Polgar, Dr Erika and Todd, Professor Andrew and Quillet, Dr Raphaelle and Dickie, Dr Allen and Gutierrez-Mecinas, Dr Maria
Authors: Alsulaiman, W. A.A., Quillet, R., Bell, A. M., Dickie, A. C., Polgár, E., Boyle, K. A., Watanabe, M., Roome, R. B., Kania, A., Todd, A., and Gutierrez-Mecinas, M.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Scientific Reports 11(1):17912
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302893Neuronal circuits for itch in the spinal dorsal hornAndrew ToddMedical Research Council (MRC)MR/S002987/1NP - Centre for Neuroscience
308174Spinal circuits underlying pathological painAndrew ToddWellcome Trust (WELLCOTR)219433/Z/19/ZNP - Centre for Neuroscience