Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors

AbstractThe human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying the ‘pain fovea’, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprDCreERT2 mouse line. We found that mouse plantar paw skin also has a low density of MrgprD+ neurites, and individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the magnification of plantar paw regions to contribute to the ‘pain fovea’.

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Sparse genetic tracing reveals regionally specific functional organization of mammalian nociceptors

eLife ◽

10.7554/elife.29507 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 9

Author(s):

William Olson ◽

Ishmail Abdus-Saboor ◽

Lian Cui ◽

Justin Burdge ◽

Tobias Raabe ◽

...

Keyword(s):

Spinal Cord ◽

Regional Differences ◽

Regional Difference ◽

Functional Organization ◽

Signal Transmission ◽

The Body ◽

Low Density ◽

Mouse Line ◽

Spinal Cord Slice ◽

And Behavior

The human distal limbs have a high spatial acuity for noxious stimuli but a low density of pain-sensing neurites. To elucidate mechanisms underlying regional differences in processing nociception, we sparsely traced non-peptidergic nociceptors across the body using a newly generated MrgprdCreERT2 mouse line. We found that mouse plantar paw skin is also innervated by a low density of Mrgprd+ nociceptors, while individual arbors in different locations are comparable in size. Surprisingly, the central arbors of plantar paw and trunk innervating nociceptors have distinct morphologies in the spinal cord. This regional difference is well correlated with a heightened signal transmission for plantar paw circuits, as revealed by both spinal cord slice recordings and behavior assays. Taken together, our results elucidate a novel somatotopic functional organization of the mammalian pain system and suggest that regional central arbor structure could facilitate the “enlarged representation” of plantar paw regions in the CNS.

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A size principle for recruitment of Drosophila leg motor neurons

eLife ◽

10.7554/elife.56754 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 6

Author(s):

Anthony W Azevedo ◽

Evyn S Dickinson ◽

Pralaksha Gurung ◽

Lalanti Venkatasubramanian ◽

Richard S Mann ◽

...

Keyword(s):

Motor Neurons ◽

Functional Organization ◽

Fruit Fly ◽

The Body ◽

Hierarchical Organization ◽

Size Principle ◽

And Behavior ◽

In Vivo Calcium Imaging ◽

The Brain

To move the body, the brain must precisely coordinate patterns of activity among diverse populations of motor neurons. Here, we use in vivo calcium imaging, electrophysiology, and behavior to understand how genetically-identified motor neurons control flexion of the fruit fly tibia. We find that leg motor neurons exhibit a coordinated gradient of anatomical, physiological, and functional properties. Large, fast motor neurons control high force, ballistic movements while small, slow motor neurons control low force, postural movements. Intermediate neurons fall between these two extremes. This hierarchical organization resembles the size principle, first proposed as a mechanism for establishing recruitment order among vertebrate motor neurons. Recordings in behaving flies confirmed that motor neurons are typically recruited in order from slow to fast. However, we also find that fast, intermediate, and slow motor neurons receive distinct proprioceptive feedback signals, suggesting that the size principle is not the only mechanism that dictates motor neuron recruitment. Overall, this work reveals the functional organization of the fly leg motor system and establishes Drosophila as a tractable system for investigating neural mechanisms of limb motor control.

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Episodic swimming in the larval zebrafish is generated by a spatially distributed spinal network with modular functional organization

Journal of Neurophysiology ◽

10.1152/jn.00233.2012 ◽

2012 ◽

Vol 108 (3) ◽

pp. 925-934 ◽

Cited By ~ 21

Author(s):

Timothy D. Wiggin ◽

Tatiana M. Anderson ◽

John Eian ◽

Jack H. Peck ◽

Mark A. Masino

Keyword(s):

Spinal Cord ◽

Functional Organization ◽

Body Wave ◽

The Body ◽

Body Segments ◽

Larval Zebrafish ◽

Spatially Distributed ◽

Spinal Segments ◽

Spinal Network ◽

Left And Right

Despite the diverse methods vertebrates use for locomotion, there is evidence that components of the locomotor central pattern generator (CPG) are conserved across species. When zebrafish begin swimming early in development, they perform short episodes of activity separated by periods of inactivity. Within these episodes, the trunk flexes with side-to-side alternation and the traveling body wave progresses rostrocaudally. To characterize the distribution of the swimming CPG along the rostrocaudal axis, we performed transections of the larval zebrafish spinal cord and induced fictive swimming using N-methyl-d-aspartate (NMDA). In both intact and spinalized larvae, bursting is found throughout the rostrocaudal extent of the spinal cord, and the properties of fictive swimming observed were dependent on the concentration of NMDA. We isolated series of contiguous spinal segments by performing multiple spinal transections on the same larvae. Although series from all regions of the spinal cord have the capacity to produce bursts, the capacity to produce organized episodes of fictive swimming has a rostral bias: in the rostral spinal cord, only 12 contiguous body segments are necessary, whereas 23 contiguous body segments are necessary in the caudal spinal cord. Shorter series of segments were often active but produced either continuous rhythmic bursting or sporadic, nonrhythmic bursting. Both episodic and continuous bursting alternated between the left and right sides of the body and showed rostrocaudal progression, demonstrating the functional dissociation of the circuits responsible for episodic structure and fine burst timing. These findings parallel results in mammalian locomotion, and we propose a hierarchical model of the larval zebrafish swimming CPG.

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Faculty Opinions recommendation of Functional organization of locomotor interneurons in the ventral lumbar spinal cord of the newborn rat.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13601956.14995056 ◽

2012 ◽

Author(s):

Serge Rossignol

Keyword(s):

Spinal Cord ◽

Functional Organization ◽

Lumbar Spinal Cord ◽

Newborn Rat ◽

Lumbar Spinal

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The neurological level of spinal cord injury and cardiovascular risk factors: a systematic review and meta-analysis

Spinal Cord ◽

10.1038/s41393-021-00678-6 ◽

2021 ◽

Author(s):

Peter Francis Raguindin ◽

Gion Fränkl ◽

Oche Adam Itodo ◽

Alessandro Bertolo ◽

Ramona Maria Zeh ◽

...

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Blood Pressure ◽

Spinal Cord ◽

Cardiovascular Risk ◽

Meta Analysis ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Cord Injury

Abstract Study design Systematic review and meta-analysis. Objective To determine the difference in cardiovascular risk factors (blood pressure, lipid profile, and markers of glucose metabolism and inflammation) according to the neurological level of spinal cord injury (SCI). Methods We searched 5 electronic databases from inception until July 4, 2020. Data were extracted by two independent reviewers using a pre-defined data collection form. The pooled effect estimate was computed using random-effects models, and heterogeneity was calculated using I2 statistic and chi-squared test (CRD42020166162). Results We screened 4863 abstracts, of which 47 studies with 3878 participants (3280 males, 526 females, 72 sex unknown) were included in the meta-analysis. Compared to paraplegia, individuals with tetraplegia had lower systolic and diastolic blood pressure (unadjusted weighted mean difference, −14.5 mmHg, 95% CI −19.2, −9.9; −7.0 mmHg 95% CI −9.2, −4.8, respectively), lower triglycerides (−10.9 mg/dL, 95% CI −19.7, −2.1), total cholesterol (−9.9 mg/dL, 95% CI −14.5, −5.4), high-density lipoprotein (−1.7 mg/dL, 95% CI −3.3, −0.2) and low-density lipoprotein (−5.8 mg/dL, 95% CI −9.0, −2.5). Comparing individuals with high- vs. low-thoracic SCI, persons with higher injury had lower systolic and diastolic blood pressure (−10.3 mmHg, 95% CI −13.4, −7.1; −5.3 mmHg 95% CI −7.5, −3.2, respectively), while no differences were found for low-density lipoprotein, serum glucose, insulin, and inflammation markers. High heterogeneity was partially explained by age, prevalent cardiovascular diseases and medication use, body mass index, sample size, and quality of studies. Conclusion In SCI individuals, the level of injury may be an additional non-modifiable cardiovascular risk factor. Future well-designed longitudinal studies with sufficient follow-up and providing sex-stratified analyses should confirm our findings and explore the role of SCI level in cardiovascular health and overall prognosis and survival.

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PSV-19 Effect of Low Nutrient Density Diet with Probiotic Mixture (B. Subtilis ms1, B. Licheniformis SF5-1, and S. Cerevisiae) Supplementation on Performance of Weaner Pigs

Journal of Animal Science ◽

10.1093/jas/skab054.318 ◽

2021 ◽

Vol 99 (Supplement_1) ◽

pp. 193-195

Author(s):

Vetriselvi Sampath ◽

Hyun Ju Park ◽

Yong min Kim ◽

Je Min Ahn ◽

Inho Kim

Keyword(s):

Body Weight ◽

Growth Performance ◽

Average Daily Gain ◽

Nutrient Digestibility ◽

The Body ◽

Interactive Effects ◽

Low Density ◽

Gas Emission ◽

Nutrient Density ◽

Weaner Pigs

Abstract BACKGROUND: A total of one hundred and forty, 28 d-old weaner pigs [Duroc x (Yorkshire x Landrace)] with initial body weight (BW) of 6.56±1.25kg were used in a six-week treatment (7 replicate pens per treatment; barrows, and 2 gilts/pen) to evaluate the effect of low nutrient density diet supplement with probiotic mixture supplementation on the growth performance, nutrient digestibility, fecal microbial, and gas emission of weaner pigs. RESULTS: Pigs fed low-density diet with probiotic mixture supplementation had linearly increased (P = 0.028, 0.014) the body weight (BW) at weeks 3, and 6. Moreover, average daily gain (ADG) was linearly improved (P=0.018, 0.014, 0.014) at week 3, 6, and overall experiment. However, there were no interactive effects found on the nutrient digestibility of dry matter (DM), nitrogen (N) and energy (E) throughout the experiment. Dietary inclusion of low-density diet with probiotic mixture supplementation has improved the fecal lactobacillus counts linearly, but E. coli was unaffected during the trail. On day 42, Ammonium gas emission was significantly decrease in pigs fed a low-density diet with probiotic mixture supplementation. However, H2S, acetic acid, and CO2 were not significantly affected by the probiotic mixture supplementation diet. CONCLUSION: Low-density diet with probiotic mixture supplementation had positively affected the growth performance, fecal microbial, and fecal gas emission on weaner pigs.

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Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

Scientific Reports ◽

10.1038/s41598-021-84667-y ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Rebecca Rani Das Gupta ◽

Louis Scheurer ◽

Pawel Pelczar ◽

Hendrik Wildner ◽

Hanns Ulrich Zeilhofer

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Functional Organization ◽

Affinity Purification ◽

Expression Patterns ◽

Inhibitory Neurons ◽

Dorsal Horn Neurons ◽

Expression Of Genes ◽

Excitatory Neurons ◽

Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

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Morphological characterization of the cholesteryl ester cycle in cultured mouse macrophage foam cells.

The Journal of Cell Biology ◽

10.1083/jcb.97.4.1156 ◽

1983 ◽

Vol 97 (4) ◽

pp. 1156-1168 ◽

Cited By ~ 95

Author(s):

D J McGookey ◽

R G Anderson

Keyword(s):

Cholesteryl Ester ◽

Lipase Activity ◽

Lipid Droplets ◽

Free Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

The Body ◽

Cyclic Process ◽

Low Density ◽

Cholesteryl Esters

Mouse peritoneal macrophages can be induced to accumulate cholesteryl esters by incubating them in the presence of acetylated low density lipoprotein. The cholesteryl esters are sequestered in neutral lipid droplets that remain in the cell even when the acetylated low density lipoprotein is removed from the culture media. Previous biochemical studies have determined that the cholesterol component of cholesteryl ester droplets constantly turns over with a half time of 24 h by a cyclic process of de-esterification and re-esterification. We have used morphologic techniques to determine the spatial relationship of cholesteryl ester, free cholesterol, and lipase activity during normal turnover and when turnover is disrupted. Lipid droplets were surrounded by numerous 7.5-10.0-nm filaments; moreover, at focal sites on the margin of each droplet there were whorles of concentrically arranged membrane that penetrated the matrix. Histochemically detectable lipase activity was associated with these stacks of membrane. Using filipin as a light and electron microscopic probe for free cholesterol, we determined that a pool of free cholesterol was associated with each lipid droplet. Following incubation in the presence of the exogenous cholesterol acceptor, high density lipoprotein, the cholesteryl ester droplets disappeared and were replaced with lipid droplets of a different lipid composition. Inhibition of cholesterol esterification caused cholesteryl ester droplets to disappear and free cholesterol to accumulate in numerous myelin-like structures in the body of the cell.

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