Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner

Mitew, Stanislaw; Gobius, Ilan; Fenlon, Laura R.; McDougall, Stuart J.; Hawkes, David; Xing, Yao Lulu; Bujalka, Helena; Gundlach, Andrew L.; Richards, Linda J.; Kilpatrick, Trevor J.; Merson, Tobias D.; Emery, Ben

doi:10.1038/s41467-017-02719-2

Cited by 260 publications

(318 citation statements)

References 56 publications

(85 reference statements)

Supporting

Mentioning

298

Contrasting

Unclassified

Order By: Relevance

“…This observation is in agreement with recent experiments showing that increasing the caliber of normally unmyelinated axons induces their myelination (Goebbels et al, ; Mayoral, Etxeberria, Shen, & Chan, ). However, it disagrees with another recent report showing that neuronal activity does not change the axon diameter of newly myelinated axons (probably glutamatergic; Mitew et al, ). On the basis of these new results, it will be probably necessary to study in details the mechanisms governing the activity‐driven adaptive myelination of specific neuronal subtypes.…”

Section: Gaba In Neuron–oligodendroglia Communicationcontrasting

confidence: 88%

Glutamate versus GABA in neuron–oligodendroglia communication

Habermacher

Angulo

Benamer

2019

Glia

View full text Add to dashboard Cite

In the central nervous system (CNS), myelin sheaths around axons are formed by glial cells named oligodendrocytes (OLs). In turn, OLs are generated by oligodendrocyte precursor cells (OPCs) during postnatal development and in adults, according to a process that depends on the proliferation and differentiation of these progenitors. The maturation of OL lineage cells as well as myelination by OLs are complex and highly regulated processes in the CNS. OPCs and OLs express an array of receptors for neurotransmitters, in particular for the two main CNS neurotransmitters glutamate and GABA, and are therefore endowed with the capacity to respond to neuronal activity. Initial studies in cell cultures demonstrated that both glutamate and GABA signaling mechanisms play important roles in OL lineage cell development and function. However, much remains to be learned about the communication of glutamatergic and GABAergic neurons with oligodendroglia in vivo. This review focuses on recent major advances in our understanding of the neuron–oligodendroglia communication mediated by glutamate and GABA in the CNS, and highlights the present controversies in the field. We discuss the expression, activation modes and potential roles of synaptic and extrasynaptic receptors along OL lineage progression. We review the properties of OPC synaptic connectivity with presynaptic glutamatergic and GABAergic neurons in the brain and consider the implication of glutamate and GABA signaling in activity‐driven adaptive myelination.

show abstract

Section: Gaba In Neuron–oligodendroglia Communicationcontrasting

confidence: 88%

Glutamate versus GABA in neuron–oligodendroglia communication

Habermacher

Angulo

Benamer

2019

Glia

View full text Add to dashboard Cite

show abstract

“…Elimination of neuronal activity by transection of the developing rat optic nerve or by intraocular TTX injection reduces the number of dividing OPCs (Barres & Raff, ), suggesting the neuronal activity is required for proliferation. In accordance with this, electrical, optogenetic, or chemogenetic stimulation of neurons in mice and rats in vivo results in increased proliferation of OPCs in the premotor cortex, the corpus callosum, and the spinal cord, and also reduces the apoptosis of OPC in some conditions (Gibson et al, ; Li, Brus‐Ramer, Martin, & McDonald, ; Mitew et al, ; Nagy et al, ). However, increased proliferation of OPCs was also observed upon sensory deprivation induced by removal of whiskers in neonatal mice (Hill, Patel, Goncalves, Grutzendler, & Nishiyama, ; Mangin et al, ) and accompanied by reduced AMPAR‐mediated thalamocortical synaptic input onto OPCs (Mangin et al, ).…”

Section: Functional Role Of Glutamate Receptors and Glutamatergic Sigmentioning

confidence: 79%

Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

Kula

Chen

Kukley

2019

Glia

View full text Add to dashboard Cite

Fast chemical synaptic transmission is a major form of neuronal communication in the nervous system of mammals. Another important, but very different, form of intercellular communication is volume transmission, which is a slower non‐synaptic signaling. The amino acid glutamate is the most abundant excitatory neurotransmitter in the nervous system, which mediates both synaptic and non‐synaptic signaling via ionotropic and metabotropic glutamate receptors. Intriguingly, neurons establish glutamatergic synapses also with oligodendrocyte precursor cells (NG2+‐glia). Moreover, neuronal activity and glutamate receptors play an important role in the development and functionality of oligodendrocytes and their precursors in vivo. Yet, molecular characteristics and functional significance of neuron–glia synapses remain poorly understood, and it is unclear how glutamate receptors mediate the effects of neuronal activity on the oligodendrocyte lineage cells. In this review, we discuss what is known with regard to synaptic and non‐synaptic glutamatergic signaling between neurons and oligodendrocyte lineage cells, what can be suggested based on the current state of knowledge, and what is fully unknown and requires new research.

show abstract

“…Second, some premyelinating processes are retracted from the axons, while others form stable myelin (Czopka, Ffrench-Constant, & Lyons, 2013). Studies using optogenetic or pharmacogenetic (DREADD) treatment to modulate neuronal activity have provided us with important information about activity-dependent myelination (Gibson et al, 2014;Mitew et al, 2018), but it is also important to check whether these results are reproduced under natural physiological conditions. In our study, we successfully observed the full formation of myelin sheaths generated by individual oligodendrocytes after remodeling.…”

Section: Discussionmentioning

confidence: 99%

Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input‐deprived axonal activities in sensory deprived mouse models

Osanai

Shimizu

Mori

et al. 2018

Glia

View full text Add to dashboard Cite

Oligodendrocytes myelinate neuronal axons to increase conduction velocity in the vertebrate central nervous system (CNS). Recent studies revealed that myelin formed on highly active axons is more stable compared to activity‐silenced axons, and length of the myelin sheath is longer in active axons as well in the zebrafish larva. However, it is unclear whether oligodendrocytes preferentially myelinate active axons compared to sensory input‐deprived axons in the adult mammalian CNS. It is also unknown if a single oligodendrocyte forms both longer myelin sheaths on active axons and shorter sheaths on input‐deprived axons after long‐term sensory deprivation. To address these questions, we applied simultaneous labeling of both neuronal axons and oligodendrocytes to mouse models of long‐term monocular eyelid suturing and unilateral whisker removal. We found that individual oligodendrocytes evenly myelinated normal and input‐deprived axons in the adult mouse CNS, and myelin sheath length on normal axons and input‐deprived axons formed by a single oligodendrocyte were comparable. Importantly, the average length of the myelin sheath formed by individual oligodendrocytes did change depending on relative abundance of normal against sensory‐input deprived axons, indicating an abundance of deprived axons near an oligodendrocyte impacts on myelination program by a single oligodendrocyte.

show abstract

Pharmacogenetic stimulation of neuronal activity increases myelination in an axon-specific manner

Cited by 260 publications

References 56 publications

Glutamate versus GABA in neuron–oligodendroglia communication

Glutamate versus GABA in neuron–oligodendroglia communication

Glutamatergic signaling between neurons and oligodendrocyte lineage cells: Is it synaptic or non‐synaptic?

Length of myelin internodes of individual oligodendrocytes is controlled by microenvironment influenced by normal and input‐deprived axonal activities in sensory deprived mouse models

Contact Info

Product

Resources

About