Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection

Gransee, Heather M.; Porras, Maria A. Gonzalez; Zhan, Wen Zhi; Sieck, Gary C.; Mantilla, Carlos B.

doi:10.1002/cne.24125

Cited by 31 publications

(40 citation statements)

References 60 publications

(150 reference statements)

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“…Both NR1 and NR2A subunits have been widely observed in rat spinal cords (Furuyama et al ; Luque et al ; Piehl et al ). We have also previously verified the presence of Grin1 mRNA expression in retrogradely labeled PhMNs in adult rats (Mantilla et al ; Gransee et al ). Activation of NMDA receptors removes a Mg 2+ channel block increasing post‐synaptic excitability (Christenson et al ; Durand ; el Manira et al ), and, given their slow receptor kinetics, provides an important substrate for temporal summation of excitatory post synaptic currents (Rekling et al ).…”

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronssupporting

confidence: 64%

“…AMPA receptors exist as heterotetramers which comprise various combinations of its four subunits GluR1‐4 (Greger et al ). Although all four subunits are present in rat spinal cords (Tolle et al ; Furuyama et al ; Tolle et al ), GluR2 mRNA is widely expressed in the spinal cord ventral horns and we have previously verified GluR2 mRNA expression in retrogradely‐labeled PhMNs in adult rats (Mantilla et al ; Gransee et al ). Of note, AMPA receptors containing GluR2 subunits (encoded by the Gria2 gene) can shape synaptic currents because of their considerably slower rates of desensitization and subsequent relatively faster recovery (Smith et al ; Funk et al ; Seeburg ).…”

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 63%

“…Probe‐ Rn‐Grin1‐C3 (Cat# 317021‐C3, Accession No: NM_001270602 Advanced Cell Diagnostics) was used to label Grin1 mRNA encoding the obligatory NR1 subunit of NMDA receptors. The Gria2 and Grin1 subunits have previously been verified as being highly expressed in rat PhMNs (Mantilla et al ; Gransee et al ).…”

Section: Methodsmentioning

confidence: 91%

“…Differences in mRNA transcript density across motor neurons of varying size likely have implications for neuroplasticity across the motor neuron pool that are of considerable interestin the context of conditions associated with altered glutamatergic neurotransmission including following spinal cord injury. In previous studies using laser‐capture microdissection of PhMNs, we found that NMDA Grin1 mRNA expression initially decreases ipsilaterally in PhMNs at 3 days after a unilateral C2 hemisection (C2SH) injury that disrupts the primary descending excitatory inputs, but then increases at 14 days post‐C2SH and 21 days post‐C2SH (Mantilla et al ; Gransee et al ). We did not find significant changes in AMPA Gria2 mRNA expression after C2SH.…”

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 90%

“…Glutamate is the main fast acting excitatory neurotransmitter at PhMNs (McCrimmon et al ; Saji and Miura ; Greer et al ; Rana et al ). Multiple reports document the presence of two key ionotropic receptors mediating glutamatergic neurotransmission at PhMNs, AMPA and NMDA receptors (Liu et al ; Chitravanshi and Sapru ; Alilain and Goshgarian ; Mantilla et al ; Gransee et al ; Mantilla et al ). In the present study, the total number of glutamatergic mRNA transcripts per PhMN varied considerably across motor neurons of varying size.…”

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 99%

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Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats

Rana

Sieck

Mantilla

2019

Journal of Neurochemistry

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The diaphragm muscle comprises various types of motor units that are recruited in an orderly fashion governed by the intrinsic electrophysiological properties (membrane capacitance as a function of somal surface area) of phrenic motor neurons (PhMNs). Glutamate is the main excitatory neurotransmitter at PhMNs and acts primarily via fast acting AMPA and N‐methyl‐D‐aspartic acid (NMDA) receptors. Differences in receptor expression may also contribute to motor unit recruitment order. We used single cell, multiplex fluorescence in situ hybridization to determine glutamatergic receptor mRNA expression across PhMNs based on their somal surface area. In adult male and female rats (n = 9) PhMNs were retrogradely labeled for analyses (n = 453 neurons). Differences in the total number and density of mRNA transcripts were evident across PhMNs grouped into tertiles according to somal surface area. A ~ 25% higher density of AMPA (Gria2) and NMDA (Grin1) mRNA expression was evident in PhMNs in the lower tertile compared to the upper tertile. These smaller PhMNs likely comprise type S motor units that are recruited first to accomplish lower force, ventilatory behaviors. In contrast, larger PhMNs with lower volume densities of AMPA and NMDA mRNA expression presumably comprise type FInt and FF motor units that are recruited during higher force, expulsive behaviors. Furthermore, there was a significantly higher cytosolic NMDA mRNA expression in small PhMNs suggesting a more important role for NMDA‐mediated glutamatergic neurotransmission at smaller PhMNs. These results are consistent with the observed order of motor unit recruitment and suggest a role for glutamatergic receptors in support of this orderly recruitment. Cover Image for this issue: doi: .

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Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronssupporting

confidence: 64%

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 63%

Section: Methodsmentioning

confidence: 91%

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 90%

Section: Glutamatergic Neurotransmission At Phrenic Motor Neuronsmentioning

confidence: 99%

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Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats

Rana

Sieck

Mantilla

2019

Journal of Neurochemistry

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Phrenic motoneuron structural plasticity across models of diaphragm muscle paralysis

Mantilla

Zhan

Gransee

et al. 2018

J of Comparative Neurology

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Structural plasticity in motoneurons may be influenced by activation history and motoneuron-muscle fiber interactions. The goal of this study was to examine morphological adaptations of phrenic motoneurons following imposed motoneuron inactivity while controlling for diaphragm muscle inactivity. Well-characterized rat models were used including unilateral C2 spinal hemisection (SH; ipsilateral phrenic motoneurons and diaphragm muscle are inactive) and tetrodotoxin phrenic nerve blockade (TTX; ipsilateral diaphragm muscle is paralyzed while phrenic motoneuron activity is preserved). We hypothesized that inactivity of phrenic motoneurons would result in a decrease in motoneuron size, consistent with a homeostatic increase in excitability. Phrenic motoneurons were retrogradely labeled by ipsilateral diaphragm muscle injection of fluorescent dextrans or cholera toxin subunit B. Following 2 weeks of diaphragm muscle paralysis, morphological parameters of labeled ipsilateral phrenic motoneurons were assessed quantitatively using fluorescence confocal microscopy. Compared to controls, phrenic motoneuron somal volumes and surface areas decreased with SH, but increased with TTX. Total phrenic motoneuron surface area was unchanged by SH, but increased with TTX. Dendritic surface area was estimated from primary dendrite diameter using a power equation obtained from 3D reconstructed phrenic motoneurons. Estimated dendritic surface area was not significantly different between control and SH, but increased with TTX. Similarly, TTX significantly increased total phrenic motoneuron surface area. These results suggest that ipsilateral phrenic motoneuron morphological adaptations are consistent with a normalization of motoneuron excitability following prolonged alterations in motoneuron activity. Phrenic motoneuron structural plasticity is likely more dependent on motoneuron activity (or descending input) than muscle fiber activity.

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Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

Fogarty¹,

Sieck²

2019

Comprehensive Physiology

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Symmorphosis is a concept of economy of biological design, whereby structural properties are matched to functional demands. According to symmorphosis, biological structures are never over designed to exceed functional demands. Based on this concept, the evolution of the diaphragm muscle (DIAm) in mammals is a tale of two structures, a membrane that separates and partitions the primitive coelomic cavity into separate abdominal and thoracic cavities and a muscle that serves as a pump to generate intra-abdominal (P ab ) and intra-thoracic (P th ) pressures. The DIAm partition evolved in reptiles from folds of the pleural and peritoneal membranes that was driven by the biological advantage of separating organs in the larger coelomic cavity into separate thoracic and abdominal cavities, especially with the evolution of aspiration breathing. The DIAm pump evolved from the advantage afforded by more effectively generation of both a negative P th for ventilation of the lungs and a positive P ab for venous return of blood to the heart and expulsive behaviors such as airway clearance, defecation, micturition, and child birth. Didactic SynopsisThe DIAm separates abdominal and thoracic cavities; thus, it is a partition, and its evolution reflects that important role in isolating organs into separate thoracic and abdominal cavities. However, the DIAm is also a muscle, and is most often described as the principal pump muscle of inspiration. However, the DIAm also serves as a pump for generating both negative P th and positive P ab in other motor behaviors. Accordingly, the evolution of the DIAm is more complex and should be considered in the context of its dual physiological roles as a partition and muscular pump. In considering DIAm evolution, we adopt the guiding concept of symmorphosis or economy of design, where biological structures are not over designed for their functional roles. Thus, this is a tale of the evolution of two diaphragms, a partition and a muscular pump that separates thoracic and abdominal cavities but also affects generation of P th and P ab .

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Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection

Cited by 31 publications

References 60 publications

Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats

Heterogeneous glutamatergic receptor mRNA expression across phrenic motor neurons in rats

Phrenic motoneuron structural plasticity across models of diaphragm muscle paralysis

Evolution and Functional Differentiation of the Diaphragm Muscle of Mammals

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