Molecular and anatomical characterization of parabrachial neurons and their axonal projections
- Howard Hughes Medical Institute, University of Washington, United States
- University of Washington, United States
Abstract
The parabrachial nucleus (PBN) is a major hub that receives sensory information from both internal and external environments. Specific populations of PBN neurons are involved in behaviors including food and water intake, nociceptive responses, breathing regulation, as well as learning and responding appropriately to threatening stimuli. However, it is unclear how many PBN neuron populations exist and how different behaviors may be encoded by unique signaling molecules or receptors. Here we provide a repository of data on the molecular identity, spatial location, and projection patterns of dozens of PBN neuron subclusters. Using single-cell RNA sequencing, we identified 21 subclusters of neurons in the PBN and neighboring regions. Multiplexed in situ hybridization showed many of these subclusters are enriched within specific PBN subregions with scattered cells in several other regions. We also provide detailed visualization of the axonal projections from 21 Cre-driver lines of mice. These results are all publicly available for download and provide a foundation for further interrogation of PBN functions and connections.
Data availability
Raw and preprocessed data for scRNA-seq: NCBI GEO accession number GSE207708Code for analysis of scRNA-Seq data: https://github.com/stuberlab/Pauli-Chen-Basiri-et-al-2022Raw and normalized data for RiboTag: NCBI GEO accession number GSE207153Images from RNAscope and all tracing experiments: Zenodo DOI: 10.5281/zenodo.6707404; https://doi.org/10.5281/zenodo.6707404
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Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal ProjectionsNCBI Gene Expression Omnibus, GSE207708.
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Gene expression profiling of Calca neurons in the parabrachial nucleus (PBN)NCBI Gene Expression Omnibus, GSE207153.
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Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal ProjectionsZenodo, DOI 10.5281/zenodo.6707404.
Article and author information
Author details
Richard D Palmiter
Funding
National Institutes of Health (R01-DA24908)
- Richard D Palmiter
National Institutes of Health (R01-DA032750)
- Garret D Stuber
National Institutes of Health (R01-DA038168)
- Garret D Stuber
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experiments were approved by the Institutional Animals Care and Use Committee at the University of Washington (Protocol #2183-02).
Copyright
© 2022, Pauli et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Molecular and anatomical characterization of parabrachial neurons and their axonal projections
eLife 11:e81868.
https://doi.org/10.7554/eLife.81868
Further reading
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- Neuroscience
Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors. To address this, we examined the role of CGRP neurons in active defensive behavior using a predator-like robot programmed to chase mice. Our electrophysiological results revealed that CGRP neurons encode the intensity of aversive stimuli through variations in firing durations and amplitudes. Optogenetic activation of CGRP neuron during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amyplifying the perception of the threat as more imminent and dangerous. In contrast, animals with inactivated CGRP neurons exhibited reduced flight responses, even when the robot was programmed to appear highly threatening during conditioning. These findings expand the understanding of CGRP neurons in the PBN as a critical alarm system, capable of dynamically regulating active defensive behaviors by amplifying threat perception, ensuring adaptive responses to varying levels of danger.
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- Neuroscience
Dendrites are crucial for receiving information into neurons. Sensory experience affects the structure of these tree-like neurites, which, it is assumed, modifies neuronal function, yet the evidence is scarce, and the mechanisms are unknown. To study whether sensory experience affects dendritic morphology, we use the Caenorhabditis elegans' arborized nociceptor PVD neurons, under natural mechanical stimulation induced by physical contacts between individuals. We found that mechanosensory signals induced by conspecifics and by glass beads affect the dendritic structure of the PVD. Moreover, developmentally isolated animals show a decrease in their ability to respond to harsh touch. The structural and behavioral plasticity following sensory deprivation are functionally independent of each other and are mediated by an array of evolutionarily conserved mechanosensory amiloride-sensitive epithelial sodium channels (degenerins). Calcium imaging of the PVD neurons in a micromechanical device revealed that controlled mechanical stimulation of the body wall produces similar calcium dynamics in both isolated and crowded animals. Our genetic results, supported by optogenetic, behavioral, and pharmacological evidence, suggest an activity-dependent homeostatic mechanism for dendritic structural plasticity, that in parallel controls escape response to noxious mechanosensory stimuli.
