Neural Circuits and Brainstem Control of Lower Urinary Tract Function
project - Identifying distinct neuronal cell types in the brainstem micturition control centers
Our and previous studies have shown voiding function to be mediated by Barrington’s nucleus (the pontine micturition center (PMC)) and periaqueductal gray (PAG) regions of the brain. We are using RNA sequencing techniques to identify the cell types in the PMC region as well as in input and output/ downstream locations. The resulting RNA expression maps help resolve the different neuronal subpopulations in the dorsal pons of the mouse, at single cell resolution.
The focus in this project is onthe neuron subpopulations most likely to control the bladder. We generate transgenic models that selectively express Cre-recombinase and that allow us to define the functional neuron subtypes for normal voiding function and with disorders of bladder function.
We collaborate with the BNORC Functional Genomics and Bioinformatics core and the excellent Spatial Transcriptomics Unit – research facilities at BIDMC, to use state of the art genomic applications for a better understanding of the heterogeneity of cells and their genetic basis, in brain regions critical for controlling lower urinary tract function. We use next generation techniques and sequencing platforms like single-nuclei RNAseq and 10X Genomics Flex assays, in combination with Visium-HD Spatial Gene expression (10x Genomics) and MERFISH (Vizgen) technology, to investigate these biological, genetic and neural circuits underlying this critical somatic function.
>> This project aims to create transcriptomic atlases of Barrington’s nucleus and the periaqueductal gray (PAG) in the brainstem, and to define functional roles for distinct neuronal populations. <<
- Funding and collaboration on this study: NIH-NIDDK DK125708 (Verstegen - PI); 2020-2025, NIH-NIDDK, P20 DK119798 (Zeidel - PI); 2018-2020
Barrington’s Nucleus Populations Send Axonal Projections to the Lumbosacral Level of the Spinal Cord. (Figure from MS accepted for publication in Nature Communications 2026).
Void Spot Assay: Micturition Video Thermography (MVT):
Chemogenetic Activation of Distinct Neuronal Populations Elicits Different Voiding Behaviors in Male and Female mice. (Figure from MS accepted for publication in Nature Communications 2026).
Useful references on RNA sequencing techniques:
1) Ecker et al., 2017 - The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas. PMCID: PMC5689454
2) Poulin et al., 2016 - Disentangling neural cell diversity using single-cell transcriptomics. PMID: 27571192
3) Bakken et al., 2018 - Single-nucleus and single-cell transcriptomes compared in matched cortical cell types. PMCID: PMC6306246
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