Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal Projections

Pauli, Jordan L; Chen, Jane; Basiri, Marcus L.; Park, Sekun; Carter, Matthew E.; Sanz, Elisenda; McKnight, G. Stanley; Stuber, Garret D.; Palmiter, Richard D.

doi:10.1101/2022.07.13.499944

Cited by 8 publications

(13 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The identity of PBN neurons engaged by CeA Htr2a neurons remains to be elucidated. The recent report on single cell transcriptomic mapping of PBN neurons will likely aid in this important endeavor (Pauli et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding

Peters

Fermani

et al. 2022

Preprint

View full text Add to dashboard Cite

SUMMARYThe central amygdala (CeA) consists of numerous genetically-defined inhibitory neurons that control defensive and appetitive behaviors including feeding. Transcriptomic signatures of cell types and their links to function remain poorly understood. Using single-nucleus RNA-sequencing, we describe nine CeA cell clusters, of which four are mostly associated with appetitive and two with aversive behaviors. To analyze the activation mechanism of appetitive CeA neurons, we characterized Serotonin receptor 2a (Htr2a)-expressing neurons (CeAHtr2a) that comprise three appetitive clusters and were previously shown to promote feeding. In vivo calcium imaging revealed that CeAHtr2aneurons are activated by fasting, the hormone ghrelin, and the presence of food. Moreover, these neurons are required for the orexigenic effects of ghrelin. Appetitive CeA neurons responsive to fasting and ghrelin project to the parabrachial nucleus (PBN) causing inhibition of target PBN neurons. These results illustrate how the transcriptomic diversification of CeA neurons relates to fasting and hormone-regulated feeding behavior.HighlightsTranscriptomics reveals four appetitive, two aversive and three unknown CeA clustersGhrelin and fasting activate CeAHtr2aneurons comprising three appetitive clustersGhrelin’s orexigenic effects require the activity of appetitive CeA neuronsCeA-→PBN inhibition is necessary for ghrelin/fasting induced feeding

show abstract

Section: Discussionmentioning

confidence: 99%

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding

Peters

Fermani

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that peptidergic neurons expressing CGRP (encoded by the Calca gene) in the external lateral parabrachial nucleus (PBel) and their direct downstream CGRP receptor-expressing neurons in the lateral subdivision of the central amygdala (CeAl) plays important roles in pain perception and threat learning in mice (Han et al, 2005; Han et al, 2015; Salmon et al, 2001; Sato et al, 2015). In addition to glutamate, CGRP neurons in the PBel (CGRP PBel ) co-express various neuropeptides, such as substance P (SP), pituitary adenylyl cyclase-activating peptide (PACAP), and neurotensin (NTS) (Kang et al, 2020; Palmiter, 2018; Pauli et al, 2022). However, the main transmitter that relays the US information in this peptidergic circuit was not known.…”

Section: Resultsmentioning

confidence: 99%

“…Since aversive sensory stimuli failed to trigger the SypSEP fluorescence increase at CGRP PBel→CeAl terminals, we investigated whether the glutamate release by CGRP PBel is dispensable in Pavlovian treat learning. To disturb glutamate release, we edited the Slc17a6 gene, which encodes Vglut2, using the CRISPR/saCas9 system (Hunker et al, 2020), based on a report showing that the Vglut2 is the main glutamate transporter in the PBel (Pauli et al, 2022). AAVs that express Cas9 and sgRNAs for Slc17a6 or Rosa26 (as control) in a Cre-dependent fashion were bilaterally injected into the PBel of Calca Cre/+ mice.…”

Section: Resultsmentioning

confidence: 99%

Novel genetically encoded tools for imaging or silencing neuropeptide release from presynaptic terminalsin vivo

Kim

Park

et al. 2023

Preprint

View full text Add to dashboard Cite

Neurons produce and release neuropeptides to communicate with one another. Despite their profound impact on critical brain functions, circuit-based mechanisms of peptidergic transmission are poorly understood, primarily due to the lack of tools for monitoring and manipulating neuropeptide release in vivo. Here, we report the development of two genetically encoded tools for investigating peptidergic transmission in behaving mice: a genetically encoded large dense core vesicle (LDCV) sensor that detects the neuropeptides release presynaptically, and a genetically encoded silencer that specifically degrades neuropeptides inside the LDCV. Monitoring and silencing peptidergic and glutamatergic transmissions from presynaptic terminals using our newly developed tools and existing genetic tools, respectively, reveal that neuropeptides, not glutamate, are the primary transmitter in encoding unconditioned stimulus during Pavlovian threat learning. These results show that our sensor and silencer for peptidergic transmission are reliable tools to investigate neuropeptidergic systems in awake behaving animals.

show abstract

“…The copyright holder for this preprint this version posted February 9, 2023. ; https://doi.org/10.1101/2023.02.08.527340 doi: bioRxiv preprint PbN neurons respond to variety of noxious stimuli (8,(12)(13)(14) and function as a hub for the relay of nociceptive information to multiple brain regions, including the periaqueductal gray, hypothalamic and thalamic nuclei, the extended amygdala, and the central amygdala (CeA) (12,(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

The parabrachial to central amygdala circuit is a key mediator of injury-induced pain sensitization

Torres-Rodriguez

Wilson

Singh

et al. 2023

Preprint

View full text Add to dashboard Cite

The spino-ponto-amygdaloid pathway is a major ascending circuit relaying nociceptive information from the spinal cord to the brain. Potentiation of excitatory synaptic transmission in the parabrachial nucleus (PbN) to central amygdala (CeA) pathway has been reported in rodent models of persistent pain. At the behavioral level, the PbN→CeA pathway has been proposed to serve as a general alarm system to potential threats that modulates pain-related escape behaviors, affective-motivational (but not somatosensory) responses to painful stimuli, aversion, and threat memory. Increased sensitivity to previously innocuous somatosensory stimulation is a hallmark of chronic pain. Whether the PbN→CeA circuit contributes to heightened sensitivity to somatosensory stimulation following an injury, however, remains unknown. Here, we demonstrate that activation of CeA-projecting PbN neurons contributes to injury-induced behavioral hypersensitivity but not baseline nociception in male and female mice. Using optogenetic assisted circuit mapping, we confirmed a functional excitatory projection from PbN→CeA that is independent of the genetic or firing identity of CeA cells. We then showed that peripheral noxious stimulation increases the expression of the neuronal activity marker c-Fos in CeA-projecting PbN neurons and chemogenetic inactivation of these cells reduces behavioral hypersensitivity in models of neuropathic and inflammatory pain without affecting baseline nociception. Lastly, we show that chemogenetic activation of CeA-projecting PbN neurons is sufficient to induce bilateral hypersensitivity without injury. Together, our results demonstrate that the PbN→CeA pathway is a key modulator pain-related behaviors that can amplify responses to somatosensory stimulation in pathological states without affecting nociception under normal physiological conditions.

show abstract

Molecular and Anatomical Characterization of Parabrachial Neurons and Their Axonal Projections

Cited by 8 publications

References 78 publications

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding

Transcriptomics reveals amygdala neuron regulation by fasting and ghrelin thereby promoting feeding

Novel genetically encoded tools for imaging or silencing neuropeptide release from presynaptic terminalsin vivo

The parabrachial to central amygdala circuit is a key mediator of injury-induced pain sensitization

Contact Info

Product

Resources

About