Abstract
Oligodendrocyte precursor cells (OPCs), a major glial cell type that gives rise to myelinating oligodendrocytes in the CNS, express calcium-permeable AMPA receptors (CP-AMPARs). Although CP-AMPARs are important for OPC proliferation and neuron-glia signaling, they render OPCs susceptible to ischemic damage in early development. We identified factors controlling the dynamic regulation of AMPAR subtypes in OPCs from rat optic nerve and mouse cerebellar cortex. We found that activation of group 1 mGluRs drove an increase in the proportion of CP-AMPARs, reflected by an increase in single-channel conductance and inward rectification. This plasticity required the elevation of intracellular calcium and used PI3K, PICK-1 and the JNK pathway. In white matter, neurons and astrocytes release both ATP and glutamate. Unexpectedly, activation of purinergic receptors in OPCs decreased CP-AMPAR expression, suggesting a capacity for homeostatic regulation. Finally, we found that stargazin-related transmembrane AMPAR regulatory proteins, which are critical for AMPAR surface expression in neurons, regulate CP-AMPAR plasticity in OPCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Newborn
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Antigens / metabolism
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Biophysical Phenomena / drug effects
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Biophysical Phenomena / genetics
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Biophysical Phenomena / physiology
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Calcium / metabolism*
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Calcium Channels / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Cycle Proteins
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cell Lineage
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Cerebellum / cytology
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Agents / pharmacology
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Female
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Galactosylceramidase / metabolism
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Gene Expression Regulation, Developmental / drug effects
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Gene Expression Regulation, Developmental / physiology
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Glutamic Acid / pharmacology
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Glycine Agents / pharmacology
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In Vitro Techniques
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology*
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Luminescent Proteins / genetics
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Male
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Membrane Potentials / drug effects
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Membrane Potentials / genetics
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Methoxyhydroxyphenylglycol / analogs & derivatives
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Methoxyhydroxyphenylglycol / pharmacology
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Mice
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Mice, Transgenic
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Mutation / genetics
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Neuronal Plasticity / genetics
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Neuronal Plasticity / physiology*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oligodendroglia / cytology
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Oligodendroglia / physiology*
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Optic Nerve / cytology
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Proteoglycans / metabolism
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Rats
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / genetics
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Stem Cells / metabolism
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Strychnine / pharmacology
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Tetrodotoxin / pharmacology
Substances
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Antigens
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Cacng2 protein, mouse
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Calcium Channels
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Carrier Proteins
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Cell Cycle Proteins
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Enzyme Inhibitors
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Excitatory Amino Acid Agents
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Glycine Agents
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Luminescent Proteins
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Nuclear Proteins
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Prkcabp protein, mouse
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Proteoglycans
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Receptors, AMPA
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chondroitin sulfate proteoglycan 4
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fluorescent protein 583
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Glutamic Acid
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Tetrodotoxin
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Methoxyhydroxyphenylglycol
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Galactosylceramidase
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Strychnine
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Calcium
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3,4-dihydroxyphenylglycol