single-cell-rna-seq-of-defined-subsets-of-retinal-ganglion-cells

Single-cell RNA-Seq of Defined Subsets of Retinal Ganglion Cells

The discovery of cell type-specific markers can provide insight into cellular function and the origins of cellular heterogeneity. With a recent push for ...

Northwestern University

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative motoneuron disease with presently no cure. Motoneuron (MN) hyperexcitability is commonly observed in ALS and is suggested to be a precursor for excitotoxic cell death. However, it is unknown whether hyperexcitability also occurs in MNs that are resistant to degeneration. Second, it is unclear whether all the MNs within homogeneous motor pools would present similar susceptibility to excitability changes since high-threshold MNs innervating fast fatigable muscle fibers selectively degenerate compared with low-threshold MNs innervating fatigue resistant slow muscle fibers. Therefore, we concurrently examined the excitability of ALS-vulnerable trigeminal motoneurons (TMNs) controlling jaw musculature and ALS-resistant oculomotor neurons (OMNs) controlling eye musculature in a well studied SOD1(G93A) ALS mouse model using in vitro patch-clamp electrophysiology at presymptomatic ages P8-P12. Our results show that hyperexcitability is not a global change among all the MNs, although mutant SOD1 is ubiquitously expressed. Instead, complex changes occur in ALS-vulnerable TMNs based on motor unit type and discharge characteristics. Firing threshold decreases among high-threshold TMNs and increases in a subpopulation of low-threshold TMNs. The latter group was identified based on their linear frequency-current responses to triangular ramp current injections. Such complex changes in MN recruitment were absent in ALS-resistant OMNs. We simulated the observed complex changes in TMN excitability using a computer-based jaw closer motor pool model. Model results suggest that hypoexcitability may indeed represent emerging disease symptomology that causes resistance in muscle force initiation. Identifying the cellular and molecular properties of these hypoexcitable cells may guide effective therapeutic strategies in ALS.

Homeostatic dysregulation in membrane properties of masticatory motoneurons compared with oculomotor neurons in a mouse model for amyotrophic lateral sclerosis.

Skeletal muscle oxidative capacity decreases and fatigability increases after spinal cord injury. Transcription factor peroxisome proliferator-activated receptor δ (PPARδ) promotes a more oxidative phenotype.

PPARδ preserves a high resistance to fatigue in the mouse medial gastrocnemius after spinal cord transection.

Recently, researchers identified a novel ganglion cell photoreceptor in vertebrates, called intrinsically photosensitive retinal ganglion cells (ipRGCs). These ipRGCs are photosensitive due to expression of a photopigment, melanopsin. Although ipRGCs were initially thought to be a uniform population of cells involved solely in subconscious, non-image forming behaviors, recent research points to a role for ipRGCs in pattern vision. Here we highlight the emerging evidence for this influence of ipRGCs on pattern vision and discuss important future directions for understanding this newly appreciated contribution of melanopsin signaling to visual processing.

Article	Year
Homeostatic dysregulation in membrane properties of masticatory motoneurons compared with oculomotor neurons in a mouse model for amyotrophic lateral sclerosis. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 25589764	2015
PPARδ preserves a high resistance to fatigue in the mouse medial gastrocnemius after spinal cord transection. Muscle & nerve\| PubMed ID: 26044200	2016
Re-evaluating the Role of Intrinsically Photosensitive Retinal Ganglion Cells: New Roles in Image-Forming Functions. Integrative and comparative biology\| PubMed ID: 27371393	2016
A Novel Role for the Visual Retinoid Cycle in Melanopsin Chromophore Regeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 27581445	2016

Takuma Sonoda

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