Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Neurophysiol
2020 Jun 01;1236:2297-2310. doi: 10.1152/jn.00105.2020.
Show Gene links
Show Anatomy links
Molecular characterization of frog vocal neurons using constellation pharmacology.
Inagaki RT, Raghuraman S, Chase K, Steele T, Zornik E, Olivera B, Yamaguchi A.
???displayArticle.abstract???
Identification and characterization of neuronal cell classes in motor circuits are essential for understanding the neural basis of behavior. It is a challenging task, especially in a non-genetic-model organism, to identify cell-specific expression of functional macromolecules. Here, we performed constellation pharmacology, calcium imaging of dissociated neurons to pharmacologically identify functional receptors expressed by vocal neurons in adult male and female African clawed frogs, Xenopus laevis. Previously we identified a population of vocal neurons called fast trill neurons (FTNs) in the amphibian parabrachial nucleus (PB) that express N-methyl-d-aspartate (NMDA) receptors and GABA and/or glycine receptors. Using constellation pharmacology, we identified four cell classes of putative fast trill neurons (pFTNs, responsive to both NMDA and GABA/glycine applications). We discovered that some pFTNs responded to the application of substance P (SP), acetylcholine (ACh), or both. Electrophysiological recordings obtained from FTNs using an ex vivo preparation verified that SP and/or ACh depolarize FTNs. Bilateral injection of ACh, SP, or their antagonists into PBs showed that ACh receptors are not sufficient but necessary for vocal production, and SP receptors play a role in shaping the morphology of vocalizations. Additionally, we discovered that the PB of adult female X. laevis also contains all the subclasses of neurons at a similar frequency as in males, despite their sexually distinct vocalizations. These results reveal novel neuromodulators that regulate X. laevis vocal production and demonstrate the power of constellation pharmacology in identifying the neuronal subtypes marked by functional expression of cell-specific receptors in non-genetic-model organisms.NEW & NOTEWORTHY Molecular profiles of neurons are critical for understanding the neuronal functions, but their identification is challenging especially in non-genetic-model organisms. Here, we characterized the functional expression of membrane macromolecules in vocal neurons of African clawed frogs, Xenopus laevis, using a technique called constellation pharmacology. We discovered that receptors for acetylcholine and/or substance P are expressed by some classes of vocal neurons, and their activation plays a role in the production of normal vocalizations.
1557945 NSF | BIO | Division of Integrative Organismal Systems (IOS), 1934386 NSF | BIO | Division of Integrative Organismal Systems (IOS), 1755423 NSF | BIO | Division of Integrative Organismal Systems (IOS), NS091977 HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS), GM48677 NIH HHS , P01 GM048677 NIGMS NIH HHS
Babski,
A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in Drosophila.
2019, Pubmed
Babski,
A GABAergic Maf-expressing interneuron subset regulates the speed of locomotion in Drosophila.
2019,
Pubmed Bass,
Central pattern generator for vocalization: is there a vertebrate morphotype?
2014,
Pubmed Bass,
Phenotypic specification of hindbrain rhombomeres and the origins of rhythmic circuits in vertebrates.
1997,
Pubmed Bonis,
A role for the Kolliker-Fuse nucleus in cholinergic modulation of breathing at night during wakefulness and NREM sleep.
2010,
Pubmed Boscan,
Neurokininergic mechanism within the lateral crescent nucleus of the parabrachial complex participates in the heart-rate response to nociception.
2005,
Pubmed Caldeira,
Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse.
2017,
Pubmed Carmignoto,
On the role of voltage-dependent calcium channels in calcium signaling of astrocytes in situ.
1998,
Pubmed Christie,
Agonists at mu-opioid, M2-muscarinic and GABAB-receptors increase the same potassium conductance in rat lateral parabrachial neurones.
1988,
Pubmed Cinelli,
Neuronal mechanisms of respiratory pattern generation are evolutionary conserved.
2013,
Pubmed Clyne,
Sex-specific control and tuning of the pattern generator for courtship song in Drosophila.
2008,
Pubmed Curtice,
Classifying neuronal subclasses of the cerebellum through constellation pharmacology.
2016,
Pubmed Del Negro,
Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation.
2005,
Pubmed Doi,
Neuromodulation and the orchestration of the respiratory rhythm.
2008,
Pubmed Dougherty,
Locomotor rhythm generation linked to the output of spinal shox2 excitatory interneurons.
2013,
Pubmed Eide,
Culture of adult mouse neurons.
2005,
Pubmed Funk,
Neuromodulation: purinergic signaling in respiratory control.
2013,
Pubmed Gibb,
MALDIquant: a versatile R package for the analysis of mass spectrometry data.
2012,
Pubmed Giniatullin,
Desensitization of nicotinic ACh receptors: shaping cholinergic signaling.
2005,
Pubmed Goulding,
Circuits controlling vertebrate locomotion: moving in a new direction.
2009,
Pubmed Grillner,
Measured motion: searching for simplicity in spinal locomotor networks.
2009,
Pubmed Hage,
On the role of the pontine brainstem in vocal pattern generation: a telemetric single-unit recording study in the squirrel monkey.
2006,
Pubmed Haque,
WT1-Expressing Interneurons Regulate Left-Right Alternation during Mammalian Locomotor Activity.
2018,
Pubmed Imperial,
A family of excitatory peptide toxins from venomous crassispirine snails: using Constellation Pharmacology to assess bioactivity.
2014,
Pubmed
,
Xenbase Iredale,
Measurement of intracellular free calcium ion concentration in cell populations using fura-2.
1995,
Pubmed Jürgens,
A study of the central control of vocalization using the squirrel monkey.
2002,
Pubmed Jürgens,
Interactions between glutamate, GABA, acetylcholine and histamine in the periaqueductal gray's control of vocalization in the squirrel monkey.
1993,
Pubmed Kelley,
Probing forebrain to hindbrain circuit functions in Xenopus.
2017,
Pubmed
,
Xenbase Kelley,
Neuroeffectors for vocalization in Xenopus laevis: hormonal regulation of sexual dimorphism.
1986,
Pubmed
,
Xenbase Kiehn,
Locomotor circuits in the mammalian spinal cord.
2006,
Pubmed Kimchi,
A functional circuit underlying male sexual behaviour in the female mouse brain.
2007,
Pubmed Konishi,
From central pattern generator to sensory template in the evolution of birdsong.
2010,
Pubmed Lambert,
Endocytosis of Activated Muscarinic m2 Receptor (m2R) in Live Mouse Hippocampal Neurons Occurs via a Clathrin-Dependent Pathway.
2018,
Pubmed Lawton,
Motor Neurons Tune Premotor Activity in a Vertebrate Central Pattern Generator.
2017,
Pubmed
,
Xenbase Mallios,
Muscarinic receptor subtypes are differentially distributed across brain stem respiratory nuclei.
1995,
Pubmed Marder,
Central pattern generators and the control of rhythmic movements.
2001,
Pubmed Meng,
Muscarinic Receptors Are Responsible for the Cholinergic Modulation of Projection Neurons in the Song Production Brain Nucleus RA of Zebra Finches.
2017,
Pubmed Mutolo,
Identification of a cholinergic modulatory and rhythmogenic mechanism within the lamprey respiratory network.
2011,
Pubmed Potter,
Androgen-induced vocal transformation in adult female African clawed frogs.
2005,
Pubmed
,
Xenbase Raghuraman,
Defining modulatory inputs into CNS neuronal subclasses by functional pharmacological profiling.
2014,
Pubmed Ramirez,
Advances in cellular and integrative control of oxygen homeostasis within the central nervous system.
2018,
Pubmed Rezával,
Activation of Latent Courtship Circuitry in the Brain of Drosophila Females Induces Male-like Behaviors.
2016,
Pubmed Rhodes,
Xenopus vocalizations are controlled by a sexually differentiated hindbrain central pattern generator.
2007,
Pubmed
,
Xenbase Rübsamen,
Control of echolocation pulses by neurons of the nucleus ambiguus in the rufous horseshoe bat, Rhinolophus rouxi. I. Single unit recordings in the ventral motor nucleus of the laryngeal nerves in spontaneously vocalizing bats.
1986,
Pubmed Schmidt,
Breathing and vocal control: the respiratory system as both a driver and a target of telencephalic vocal motor circuits in songbirds.
2012,
Pubmed Shao,
Central cholinergic regulation of respiration: nicotinic receptors.
2009,
Pubmed Shao,
Alpha4* nicotinic receptors in preBotzinger complex mediate cholinergic/nicotinic modulation of respiratory rhythm.
2008,
Pubmed
,
Xenbase Silkstone,
Dissimilar interaction between dopaminergic and cholinergic systems in the initiation of emission of 50-kHz and 22-kHz vocalizations.
2020,
Pubmed Sweeney,
Harnessing vocal patterns for social communication.
2014,
Pubmed
,
Xenbase Teichert,
Using constellation pharmacology to define comprehensively a somatosensory neuronal subclass.
2014,
Pubmed Teichert,
Characterization of two neuronal subclasses through constellation pharmacology.
2012,
Pubmed Wan,
Unraveling a molecular determinant for clathrin-independent internalization of the M2 muscarinic acetylcholine receptor.
2015,
Pubmed Yamaguchi,
Functional specialization of male and female vocal motoneurons.
2003,
Pubmed
,
Xenbase Yu,
Endogenous serotonin acts on 5-HT2C-like receptors in key vocal areas of the brain stem to initiate vocalizations in Xenopus laevis.
2010,
Pubmed
,
Xenbase Zornik,
Coding rate and duration of vocalizations of the frog, Xenopus laevis.
2012,
Pubmed
,
Xenbase
