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
-
Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal ProjectionsNCBI Gene Expression Omnibus, GSE207708.
-
Gene expression profiling of Calca neurons in the parabrachial nucleus (PBN)NCBI Gene Expression Omnibus, GSE207153.
-
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.
Metrics
-
- 8,032
- views
-
- 1,098
- downloads
-
- 74
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Molecular and anatomical characterization of parabrachial neurons and their axonal projections
eLife 11:e81868.
https://doi.org/10.7554/eLife.81868
Further reading
-
- Neuroscience
Studying infant minds with movies is a promising way to increase engagement relative to traditional tasks. However, the spatial specificity and functional significance of movie-evoked activity in infants remains unclear. Here, we investigated what movies can reveal about the organization of the infant visual system. We collected fMRI data from 15 awake infants and toddlers aged 5–23 months who attentively watched a movie. The activity evoked by the movie reflected the functional profile of visual areas. Namely, homotopic areas from the two hemispheres responded similarly to the movie, whereas distinct areas responded dissimilarly, especially across dorsal and ventral visual cortex. Moreover, visual maps that typically require time-intensive and complicated retinotopic mapping could be predicted, albeit imprecisely, from movie-evoked activity in both data-driven analyses (i.e. independent component analysis) at the individual level and by using functional alignment into a common low-dimensional embedding to generalize across participants. These results suggest that the infant visual system is already structured to process dynamic, naturalistic information and that fine-grained cortical organization can be discovered from movie data.
-
- Neuroscience
Outcomes can vary even when choices are repeated. Such ambiguity necessitates adjusting how much to learn from each outcome by tracking its variability. The medial prefrontal cortex (mPFC) has been reported to signal the expected outcome and its discrepancy from the actual outcome (prediction error), two variables essential for controlling the learning rate. However, the source of signals that shape these coding properties remains unknown. Here, we investigated the contribution of cholinergic projections from the basal forebrain because they carry precisely timed signals about outcomes. One-photon calcium imaging revealed that as mice learned different probabilities of threat occurrence on two paths, some mPFC cells responded to threats on one of the paths, while other cells gained responses to threat omission. These threat- and omission-evoked responses were scaled to the unexpectedness of outcomes, some exhibiting a reversal in response direction when encountering surprising threats as opposed to surprising omissions. This selectivity for signed prediction errors was enhanced by optogenetic stimulation of local cholinergic terminals during threats. The enhanced threat-evoked cholinergic signals also made mice erroneously abandon the correct choice after a single threat that violated expectations, thereby decoupling their path choice from the history of threat occurrence on each path. Thus, acetylcholine modulates the encoding of surprising outcomes in the mPFC to control how much they dictate future decisions.
