Unique Molecular Characteristics of Visceral Afferents Arising from Different Levels of the Neuraxis: Location of Afferent Somata Predicts Function and Stimulus Detection Modalities

Meerschaert, Kimberly A.; Adelman, Peter; Friedman, Richard B.; Albers, Kathryn M.; Koerber, H. Richard; Davis, Brian M.

doi:10.1523/jneurosci.1426-20.2020

Cited by 38 publications

(26 citation statements)

References 74 publications

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“…This agrees with previous results (Fajardo et al, 2008). In alignment with the very low expression of TRPM8 in VG shown in this study as well as by others (Kupari et al, 2019;Meerschaert et al, 2020;Nassenstein et al, 2008), we further showed that TRPM8 plays a minor role in the mechanism of cold transduction in mouse VG, a role that is probably restricted to the jugular part of the vagal ganglion complex.…”

Section: Comparison Of Cold Sensing Mechanisms In Mouse Vg and Tgsupporting

confidence: 93%

“…TRPA1 plays a minor role, mainly in high threshold CS neurons. These functional differences in cold sensitivity find a molecular correlate in recent transcriptomic studies indicating a strong segregation in the molecular profile of somatic (DRG, TG) and vagal neurons (Kupari et al, 2019;Meerschaert et al, 2020;Nguyen et al, 2017;Zeisel et al, 2018), consistent with their different developmental origin (Baker, 2005). Our reanalysis of published single-cell transcriptomic data for mouse TG and VG found that TG had fewer TRPA1 + neurons than VG (13.3% vs 19.8%), and their expression level, calculated as reads per million (RPM) for mean Trpa1 expression normalized to RMP values for actin beta (Actb), was also higher in VG (0.558 vs 0.217).…”

Section: Comparison Of Cold Sensing Mechanisms In Mouse Vg and Tgmentioning

confidence: 65%

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Transduction mechanisms for cold temperature in mouse trigeminal and vagal ganglion neurons innervating different peripheral organs

Gers-Barlag

Hernández-Ortego

Quintero

et al. 2021

Preprint

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Thermal signals are critical elements in the operation of interoceptive and exteroceptive neural circuits, essential for triggering thermally-driven reflexes and conscious behaviors. A fraction of cutaneous and visceral sensory endings are activated by cold temperatures. Compared to somatic (DRG and TG) neurons, little is known about the mechanisms underlying cold sensitivity of visceral vagal neurons. We used pharmacological and genetic tools for a side-by-side characterization of cold-sensitive (CS) neurons in adult mouse trigeminal (TG) and vagal ganglia (VG).We found that CS neurons are more abundant in VG than in TG. In both ganglia, sensitivity to cold varied widely and was enhanced by the potassium channel blocker 4-AP. The majority of CS neurons in VG co-express TRPA1 markers and cold-evoked responses are severely blunted in Trpa1 KO mice, with little impact of TRPM8 deletion or pharmacological TRPM8 blockade. Consistent with these findings, the expression of TRPM8-positive neurons was low in VG and restricted to the rostral jugular ganglion. In vivo retrograde labelling of airway-innervating vagal neurons demonstrated their enhanced cold sensitivity and a higher expression of TRPA1 compared to neurons innervating the stomach wall. In contrast, the majority of CS TG neurons co-express TRPM8 markers and their cold sensitivity is reduced after TRPM8 deletion or blockade. However, pharmacological or genetic reduction of TRPA1 showed that these channels contribute significantly to their cold sensitivity in TG. In both ganglia, a fraction of CS neuron respond to cooling by a mechanism independent of TRPA1 or TRPM8 yet to be characterized.

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Section: Comparison Of Cold Sensing Mechanisms In Mouse Vg and Tgsupporting

confidence: 93%

Section: Comparison Of Cold Sensing Mechanisms In Mouse Vg and Tgmentioning

confidence: 65%

Transduction mechanisms for cold temperature in mouse trigeminal and vagal ganglion neurons innervating different peripheral organs

Gers-Barlag

Hernández-Ortego

Quintero

et al. 2021

Preprint

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“…An important aspect of our approach is that in visceral afferents CTB identifies all major populations of sensory neurons ( Robertson et al, 1992 ; Wang et al, 1998 ), unlike the somatic afferent system where CTB preferentially labels the myelinated class ( Robertson and Grant, 1989 ; Robertson et al, 1991 ). Electrophysiological and immunohistochemical studies have demonstrated specific features of myelinated (A-δ) and unmyelinated (C) classes of bladder and urethra afferents in rats ( Yoshimura et al, 1998 , 2003 ; Forrest et al, 2013 ; Danziger and Grill, 2016 ; Meerschaert et al, 2020 ), noting that the proportion considered to be myelinated varies across approaches and studies. We verified the uptake of CTB by both populations in our study, further showing that a major nociceptive subclass was labeled, identified by TRPV1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…The aims of this study were to comprehensively map bladder and urethra afferents in the lumbosacral cord of adult male and female rats. No unique molecular markers are currently available to selectively visualize bladder or urethral afferents, although recent transcriptome analyses of mouse DRGs have defined several clusters of genes that show high expression in bladder afferents and several differences in expression level from colonic afferents ( Meerschaert et al, 2020 ). Neural tract tracing, therefore, continues to be the most robust approach for visualizing specific nerve-organ connectivity.…”

Section: Introductionmentioning

confidence: 99%

Regional Targeting of Bladder and Urethra Afferents in the Lumbosacral Spinal Cord of Male and Female Rats: A Multiscale Analysis

Fuller-Jackson

Osborne

Keast

2021

eNeuro

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Sensorimotor circuits of the lumbosacral spinal cord are required for lower urinary tract (LUT) regulation as well as being engaged in pelvic pain states. To date, no molecular markers have been identified to enable specific visualization of LUT afferents, which are embedded within spinal cord segments that also subserve somatic functions. Moreover, previous studies have not fully investigated the patterning within or across spinal segments, compared afferent innervation of the bladder and urethra, or explored possible structural sex differences in these pathways. We have addressed these questions in adult Sprague Dawley rats, using intramural microinjection of the tract tracer, B subunit of cholera toxin (CTB). Afferent distribution was analyzed within individual sections and 3D reconstructions from sections across four spinal cord segments (L5-S2), and in cleared intact spinal cord viewed with light sheet microscopy. Simultaneous mapping of preganglionic neurons showed their location throughout S1 but restricted to the caudal half of L6. Afferents from both LUT regions extended from L5 to S2, even where preganglionic motor pathways were absent. In L6 and S1, most afferents were associated with the sacral preganglionic nucleus (SPN) and sacral dorsal commissural nucleus (SDCom), with very few in the superficial laminae of the dorsal horn. Spinal innervation patterns by bladder and urethra afferents were remarkably similar, likewise the patterning in male and female rats. In conclusion, microscale to macroscale mapping has identified distinct features of LUT afferent projections to the lumbosacral cord and provided a new anatomic approach for future studies on plasticity, injury responses, and modeling of these pathways.

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“…Here we modified a cost-effective focal CRD (fCRD) method first developed by Annahazi et al (Annahazi et al, 2012). The GI tract is dually innervated by spinal and vagal sensory neurons residing in dorsal root ganglia (DRGs) and nodose ganglia, respectively, and activation of vagal afferents is capable of producing aversive feeling as well (Furuta et al, 2012; Gebhart and Bielefeldt, 2016; Lamb et al, 2003; Meerschaert et al, 2020; Randich and Gebhart, 1992). Our goal was to study spinal substrates transmitting aversive visceral information.…”

Section: Resultsmentioning

confidence: 99%

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

Lin

2022

Preprint

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Visceral pain is among the most prevalent and bothersome forms of chronic pain, but their transmission in the spinal cord is still poorly understood. Here we used a focal colorectal distention (fCRD) method to drive visceromotor responses (VMRs) plus affective pain-indicative aversive learning. We first found that spinal CCK neurons were necessary for noxious fCRD to drive both VMRs and aversion. We next showed that spinal VGLUT3 neurons mediate affective visceral allodynia, whose ablation caused loss of aversion evoked by low-intensity fCRD in mice with gastrointestinal (GI) inflammation or spinal circuit disinhibition. Importantly, these neurons are dispensable for driving VMRs. Anatomically, VGLUT3 neurons send projection to the parabrachial nuclei, whose photoactivation sufficiently generated aversion in mice with GI inflammation. Our studies suggest the presence of different spinal substrates that transmit nociceptive versus affective dimensions of visceral sensory information.

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Unique Molecular Characteristics of Visceral Afferents Arising from Different Levels of the Neuraxis: Location of Afferent Somata Predicts Function and Stimulus Detection Modalities

Cited by 38 publications

References 74 publications

Transduction mechanisms for cold temperature in mouse trigeminal and vagal ganglion neurons innervating different peripheral organs

Transduction mechanisms for cold temperature in mouse trigeminal and vagal ganglion neurons innervating different peripheral organs

Regional Targeting of Bladder and Urethra Afferents in the Lumbosacral Spinal Cord of Male and Female Rats: A Multiscale Analysis

Spinal VGLUT3 lineage neurons drive visceral mechanical allodynia but not visceromotor reflexes

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