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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Recognizing goal-directed actions is a computationally challenging task, requiring not only the visual analysis of body movements, but also analysis of how these movements causally impact, and thereby induce a change in, those objects targeted by an action. We tested the hypothesis that the analysis of body movements and the effects they induce relies on distinct neural representations in superior and anterior inferior parietal lobe (SPL and aIPL). In four fMRI sessions, participants observed videos of actions (e.g. breaking stick, squashing plastic bottle) along with corresponding point-light-display (PLD) stick figures, pantomimes, and abstract animations of agent–object interactions (e.g. dividing or compressing a circle). Cross-decoding between actions and animations revealed that aIPL encodes abstract representations of action effect structures independent of motion and object identity. By contrast, cross-decoding between actions and PLDs revealed that SPL is disproportionally tuned to body movements independent of visible interactions with objects. Lateral occipitotemporal cortex (LOTC) was sensitive to both action effects and body movements. These results demonstrate that parietal cortex and LOTC are tuned to physical action features, such as how body parts move in space relative to each other and how body parts interact with objects to induce a change (e.g. in position or shape/configuration). The high level of abstraction revealed by cross-decoding suggests a general neural code supporting mechanical reasoning about how entities interact with, and have effects on, each other.
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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 neurons during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amplifying 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, and ensuring adaptive responses to varying levels of danger.
