Molecular ontology of the parabrachial nucleus

Karthik, Samyukta; Huang, Dake; Delgado, Yaritza; Laing, Justin J.; Peltekian, Lila; Iverson, Gabrielle N.; Grady, Fillan; Miller, Rebecca L.; McCann, Corey M.; Fritzsch, Bernd; Iskusnykh, Igor Y.; Chizhikov, Victor V.; Geerling, Joel C.

doi:10.1002/cne.25307

Cited by 36 publications

(66 citation statements)

References 226 publications

(407 reference statements)

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“…Rostral glutamatergic KF neurons express FoxP2 (Forkhead box protein P2 ) (Geerling et al ., 2017; Karthik et al ., 2022), whereas MOR-expressing glutamatergic neurons in the lateral parabrachial area that project to the forebrain express Calca, a gene that encodes the neuropeptide calcitonin gene-related peptide (CGRP) (Huang et al ., 2021). Considering this, we performed immunohistochemistry for FoxP2 and CGRP on Oprm1+ KF neurons projecting to the ventrolateral medulla.…”

Section: Resultsmentioning

confidence: 99%

“…We found that MOR-expressing dorsolateral pontine neurons that project to the ventrolateral medulla are distinct from CGRP-expressing neurons (Figure 6), although a small population of CGRP-expressing, ventrolateral medulla projecting neurons have been reported (Huang et al ., 2021). Instead, the ventrolateral medulla projecting dorsolateral pontine neurons expressed FoxP2 (Figure 6), and may constitute the population of glutamatergic FoxP2 and Lmx1b neurons recently described in the rostral KF (Karthik et al ., 2022).…”

Section: Discussionmentioning

confidence: 95%

“…Although effects of MORs in the lateral parabrachial and KF areas appear similar, mechanisms likely differ since the neuronal populations have different projection patterns (Geerling et al ., 2017; Huang et al ., 2021) and are involved in different behaviors besides breathing, especially the lateral parabrachial area (Campos et al ., 2018; Chen et al ., 2018); Liu et al ., 2022). In addition, the distinction between KF and lateral parabrachial area is not clear cut, though recent description of transcription factor expression in the dorsolateral pons provides opportunity to improve this (Karthik et al ., 2022). MORs in KF neurons could reduce respiratory rate by decreasing excitatory input to the preBötC, as shown here.…”

Section: Discussionmentioning

confidence: 99%

“…The BötC, preBötC and rVRG can be distinguished using the inferior olives, nucleus ambiguus, and nucleus tractus solitarius as medullary landmarks (Franklin & Paxinos, 2008; Varga et al ., 2020). The KF is located bilaterally in the dorsolateral pons, just ventrolateral to the tip of the superior cerebellar peduncle and medial of the middle cerebellar peduncle (Varga et al ., 2020; Karthik et al ., 2022).…”

Section: Methodsmentioning

confidence: 99%

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Opioid Suppression of an Excitatory Pontomedullary Respiratory Circuit by Convergent Mechanisms

Bateman

Levitt

2022

Preprint

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Opioids depress breathing by inhibition of inter-connected respiratory nuclei in the pons and medulla. Mu opioid receptor (MOR) agonists directly hyperpolarize a population of neurons in the dorsolateral pons, particularly the Kölliker-Fuse (KF) nucleus, that are key mediators of opioid-induced respiratory depression. However, the projection target and synaptic connections of MOR-expressing KF neurons is unknown. Here, we used retrograde labeling and brain slice electrophysiology to determine that MOR-expressing KF neurons project to respiratory nuclei in the ventrolateral medulla, including the pre-Bötzinger complex (preBötC) and rostral ventral respiratory group (rVRG). These medullary projecting, MOR-expressing dorsolateral pontine neurons express FoxP2 and are distinct from calcitonin gene-related peptide-expressing lateral parabrachial neurons. Furthermore, dorsolateral pontine neurons release glutamate onto excitatory preBötC and rVRG neurons via monosynaptic projections, which is inhibited by presynaptic opioid receptors. The excitatory preBötC and rVRG neurons receiving MOR-sensitive glutamatergic synaptic input from the dorsolateral pons are themselves hyperpolarized by opioids. Thus, opioids can synergistically inhibit this excitatory pontomedullary respiratory circuit by three distinct mechanisms—somatodendritic MORs on dorsolateral pontine and ventrolateral medullary neurons and presynaptic MORs on dorsolateral pontine neuron terminals in the ventrolateral medulla—all of which could contribute to opioid-induced respiratory depression.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Opioid Suppression of an Excitatory Pontomedullary Respiratory Circuit by Convergent Mechanisms

Bateman

Levitt

2022

Preprint

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“…In the mouse, its distribution throughout the brain has been analyzed (Huang et al 2013). Functionally, among others, it has been implicated in the development of the neocortex in both intracortical (through the corpus callosum) and subcortical projection neurons (Alcamo et al 2008;Britanova et al 2008;Leone et al 2015;McKenna et al 2015), the regionalization of the retrosplenial cortex (Zhang et al 2020), the development of different hypothalamic subpopulations (Kurrasch et al 2007;Blackshaw et al 2010;Bedont et al 2015;Ferran et al 2015;Glendining et al 2020), in particular in the speci cation of dopaminergic neurons in the arcuate nucleus of the hypothalamus (Zhang et al 2021), and recently it has been implicated in the function of the parabrachial area (Fu et al 2019;Jarvie et al 2021;Karthik et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Expression of Satb2 in adult brain of key non-mammalian vertebrates: insights from evolution

Lozano

López

Morona

et al. 2022

Preprint

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Satb2 is a transcription factor with functional and regulatory mechanisms, and post-translational modifications highly conserved in mammals. However, although its distribution has been analyzed in the mouse brain, there are few data in other non-mammal models. Therefore, in the present study we have analyzed the immunolocalization of Satb2 in the brain of adult specimens of different models at key evolutionary points of vertebrate diversification, including representative species of sarcopterygians and actinopterygians. In addition, we used other neuronal markers of highly conserved populations in the vertebrate brain, such as catecholaminergic, serotonergic and Otp populations, involved in the specificity of certain brain areas. The neuroanatomical pattern of Satb2, interpreted according to the current prosomeric model, serves to identify brain regions and compare them among the studied species, and with previous reported data, mainly for amniotes. We identified that Satb2 expressions have similar topologies in the subpallium of models studied, whereas striking differences were found in the pallium between sarcopterygian and actinopterygian vertebrates. Only the turtle showed expression in the dorsal derivatives of the pallium, specifically in the dorsal cortex, only scattered in Xenopus, whereas the lateral derivatives of the pallium expressed Satb2 in sarcopterygians, but not in actinopterygians. In the medial amygdala, or homologous structures, all models expressed Satb2, but only tetrapods also co-expressed Otp, probably originating from the paraventricular hypothalamic region, since only in those models a minor population of Satb2/Otp cells was also detected. In the caudal telencephalon, all models showed significant expression in the preoptic area, including the acroterminal domain of this region, where Satb2-expressing cells were dopaminergic. In the alar hypothalamus, all models showed Satb2 in the subparaventricular area, whereas in the basal hypothalamus only sarcopterygians showed a significant population in the tuberal hypothalamus, doubly labeled with Otp only in lungfish. The diencephalon of sarcopterygians showed Satb2 labeling in the prethalamus, and only turtles and lungfish showed expression in the thalamus. At midbrain levels, the optic tectum housed scattered Satb2 cells exclusively in turtles, while the expression along the rostrocaudal reticular formation and parabrachial nucleus was a conserved feature of sarcopterygians. The neuroanatomical pattern of Satb2 revealed important differences between sarcopterygians and actinopterygians, and these divergences may be related to the distinct functional involvement of Satb2 in the acquisition of various neural phenotypes and in the establishment of connectivity of these cells.

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Molecular ontology of the parabrachial nucleus

Karthik

Huang

Delgado

et al. 2022

J of Comparative Neurology

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Diverse neurons in the parabrachial nucleus (PB) communicate with widespread brain regions. Despite evidence linking them to a variety of homeostatic functions, it remains difficult to determine which PB neurons influence which functions because their subpopulations intermingle extensively. An improved framework for identifying these intermingled subpopulations would help advance our understanding of neural circuit functions linked to this region. Here, we present the foundation of a developmental‐genetic ontology that classifies PB neurons based on their intrinsic, molecular features. By combining transcription factor labeling with Cre fate‐mapping, we find that the PB is a blend of two, developmentally distinct macropopulations of glutamatergic neurons. Neurons in the first macropopulation express Lmx1b (and, to a lesser extent, Lmx1a) and are mutually exclusive with those in a second macropopulation, which derive from precursors expressing Atoh1. This second, Atoh1‐derived macropopulation includes many Foxp2‐expressing neurons, but Foxp2 also identifies a subset of Lmx1b‐expressing neurons in the Kölliker–Fuse nucleus (KF) and a population of GABAergic neurons ventrolateral to the PB (“caudal KF”). Immediately ventral to the PB, Phox2b‐expressing glutamatergic neurons (some coexpressing Lmx1b) occupy the KF, supratrigeminal nucleus, and reticular formation. We show that this molecular framework organizes subsidiary patterns of adult gene expression (including Satb2, Calca, Grp, and Pdyn) and predicts output projections to the amygdala (Lmx1b), hypothalamus (Atoh1), and hindbrain (Phox2b/Lmx1b). Using this molecular ontology to organize, interpret, and communicate PB‐related information could accelerate the translation of experimental findings from animal models to human patients.

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Molecular ontology of the parabrachial nucleus

Cited by 36 publications

References 226 publications

Opioid Suppression of an Excitatory Pontomedullary Respiratory Circuit by Convergent Mechanisms

Opioid Suppression of an Excitatory Pontomedullary Respiratory Circuit by Convergent Mechanisms

Expression of Satb2 in adult brain of key non-mammalian vertebrates: insights from evolution

Molecular ontology of the parabrachial nucleus

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