Excitatory and inhibitory innervation of the mouse orofacial motor nuclei: A stereological study

Faunes, Macarena; Oñate-Ponce, Alejandro; Fernández-Collemann, Sara; Henny, Pablo

doi:10.1002/cne.23862

Cited by 15 publications

(9 citation statements)

References 97 publications

(203 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Local interneurons and descending projections also contribute to MN excitation, and elimination of these VGluT2 + inputs also has been shown to be protective in the SOD1 G93A mouse (59). In ALS, some vulnerable MNs do not receive synaptic input from I A afferent fibers (60,61), suggesting that excitotoxicity from I A afferents alone does not result in MN degeneration. This observation is consistent with our model that excitatory inputs generally contribute to MN degeneration in ALS.…”

Section: Discussionmentioning

confidence: 99%

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS

Lalancette–Hébert

Sharma

Lyashchenko

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

106

View full text Add to dashboard Cite

The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (I A ) fibers. Elimination of these synapses protects α-MNs in the SOD1 mutant, implicating this excitatory input in MN degeneration. Moreover, reduced I A activation by targeted reduction of γ-MNs in SOD1G93A mutants delays symptom onset and prolongs lifespan, demonstrating a pathogenic role of surviving γ-MNs in ALS. This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS.ALS | motor neuron disease | gamma motor neuron | fusimotor A myotrophic lateral sclerosis (ALS) is a fatal disorder characterized by selective motor neuron (MN) degeneration in the brain and spinal cord (1). Not all MN subtypes are equally vulnerable in ALS, and specific subpopulations of MNs, including neurons in the oculomotor and Onuf's nuclei, are preserved even at late stages of disease (2-8). The sparing of these motor pools in ALS is complete, but within the motor pools that are affected the degree to which distinct functional subtypes of MNs are vulnerable varies: fast-fatigable motor neurons are the first to degenerate in ALS patients (9) and in mutant SOD1 mice (10, 11), followed by fatigue-resistant motor units, whereas slow motor units are preserved until late in the course of the disease (12). The reason for the selective vulnerability of distinct subpopulations of MNs in ALS is not known, but factors that determine the unique features of individual MN subtypes, including their size, morphology, and membrane properties, may play a role. In addition, the factors that influence MN vulnerability in ALS may relate to the organization and function of synaptic inputs on each MN subtype that regulate MN activity and control motor output. How the connectivity of MNs within complex motor circuits influences their relative vulnerability in ALS is not known.Extraocular muscles composed of multiple (fast-, intermediate-, and slow-twitch) fiber types (13) and innervated by ALS

show abstract

Section: Discussionmentioning

confidence: 99%

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS

Lalancette–Hébert

Sharma

Lyashchenko

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

106

View full text Add to dashboard Cite

show abstract

“…For the estimation of Dcx+, BrdU, and Ki67+ cell density (cells/mm 3 ) in the dentate gyrus, one set of serial sections (see tissue sectioning) from each animal was used. The optical dissector method was used to estimate Dcx+, BrdU+, and Ki67+ cells in the granule cell layer of GFP+ sections using the optical fractionator workflow of the Stereo Investigator software (MBF Bioscience, Williston, VT) . Briefly, after tracing the contours of the granule cell layer of green areas of the dorsal and ventral DG at 4x magnification (Nikon Eclipse Ci‐L; N.A.…”

Section: Methodsmentioning

confidence: 99%

“…The area of each disector box counting frame was 100 × 100 μm, using a grid size of 100 × 100, therefore sampling 100% of the area. These parameters yielded a Gundersen coefficient of error (CE) ranging between 0.05 and 0.09, which are values acceptable for stereological analyses . A minimum of three sections per animal was analyzed for each serial section.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling

et al. 2019

Self Cite

View full text Add to dashboard Cite

In the adult hippocampus, new neurons are generated in the dentate gyrus. The Wnt signaling pathway regulates this process, but little is known about the endogenous Wnt ligands involved. We investigated the role of Wnt5a on adult hippocampal neurogenesis. Wnt5a regulates neuronal morphogenesis during embryonic development, and maintains dendritic architecture of pyramidal neurons in the adult hippocampus. Here, we determined that Wnt5a knockdown in the mouse dentate gyrus by lentivirus‐mediated shRNA impaired neuronal differentiation of progenitor cells, and reduced dendritic development of adult‐born neurons. In cultured adult hippocampal progenitors (AHPs), Wnt5a knockdown reduced neuronal differentiation and morphological development of AHP‐derived neurons, whereas treatment with Wnt5a had the opposite effect. Interestingly, no changes in astrocytic differentiation were observed in vivo or in vitro, suggesting that Wnt5a does not affect fate‐commitment. By using specific inhibitors, we determined that Wnt5a signals through CaMKII to induce neurogenesis, and promotes dendritic development of newborn neurons through activating Wnt/JNK and Wnt/CaMKII signaling. Our results indicate Wnt5a as a niche factor in the adult hippocampus that promotes neuronal differentiation and development through activation of noncanonical Wnt signaling pathways.

show abstract

“…For example, there is an early disruption of NMJs of MNs that innervate the cutaneous maximus muscle (a type II muscle) (by P60 already) in the SOD1 G93A mouse [ 71 ], although these MN somas lack monosynaptic sensory afferent proprioceptive input altogether [ 72 ]. Likewise, only a few hypoglossal MNs actually have VGLUT1 + synapses [ 73 ], although they are vulnerable in ALS. Altogether, I A sensory input could contribute to the difference between αMN and γMN sensitivity in ALS as it may exacerbate hyperexcitability of αMNs, but it does not appear to underlie the vulnerability of αMNs fundamentally.…”

Section: Motor Neuronsmentioning

confidence: 99%

The Cell Autonomous and Non-Cell Autonomous Aspects of Neuronal Vulnerability and Resilience in Amyotrophic Lateral Sclerosis

Schweingruber

Hedlund

2022

Biology

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is defined by the loss of upper motor neurons (MNs) that project from the cerebral cortex to the brain stem and spinal cord and of lower MNs in the brain stem and spinal cord which innervate skeletal muscles, leading to spasticity, muscle atrophy, and paralysis. ALS involves several disease stages, and multiple cell types show dysfunction and play important roles during distinct phases of disease initiation and progression, subsequently leading to selective MN loss. Why MNs are particularly vulnerable in this lethal disease is still not entirely clear. Neither is it fully understood why certain MNs are more resilient to degeneration in ALS than others. Brain stem MNs of cranial nerves III, IV, and VI, which innervate our eye muscles, are highly resistant and persist until the end-stage of the disease, enabling paralyzed patients to communicate through ocular tracking devices. MNs of the Onuf’s nucleus in the sacral spinal cord, that innervate sphincter muscles and control urogenital functions, are also spared throughout the disease. There is also a differential vulnerability among MNs that are intermingled throughout the spinal cord, that directly relate to their physiological properties. Here, fast-twitch fatigable (FF) MNs, which innervate type IIb muscle fibers, are affected early, before onset of clinical symptoms, while slow-twitch (S) MNs, that innervate type I muscle fibers, remain longer throughout the disease progression. The resilience of particular MN subpopulations has been attributed to intrinsic determinants and multiple studies have demonstrated their unique gene regulation and protein content in health and in response to disease. Identified factors within resilient MNs have been utilized to protect more vulnerable cells. Selective vulnerability may also, in part, be driven by non-cell autonomous processes and the unique surroundings and constantly changing environment close to particular MN groups. In this article, we review in detail the cell intrinsic properties of resilient and vulnerable MN groups, as well as multiple additional cell types involved in disease initiation and progression and explain how these may contribute to the selective MN resilience and vulnerability in ALS.

show abstract

Excitatory and inhibitory innervation of the mouse orofacial motor nuclei: A stereological study

Cited by 15 publications

References 97 publications

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS

Gamma motor neurons survive and exacerbate alpha motor neuron degeneration in ALS

Wnt5a promotes differentiation and development of adult-born neurons in the hippocampus by noncanonical Wnt signaling

The Cell Autonomous and Non-Cell Autonomous Aspects of Neuronal Vulnerability and Resilience in Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About