Abstract
NMDA receptor (NMDAR) activation can alter synaptic strength by regulating transmitter release from a variety of neurons in the CNS. As NMDARs are permeable to Ca(2+) and monovalent cations, they could alter release directly by increasing presynaptic Ca(2+) or indirectly by axonal depolarization sufficient to activate voltage-sensitive Ca(2+) channels (VSCCs). Using two-photon microscopy to measure Ca(2+) excursions, we found that somatic depolarization or focal activation of dendritic NMDARs elicited small Ca(2+) transients in axon varicosities of cerebellar stellate cell interneurons. These axonal transients resulted from Ca(2+) entry through VSCCs that were opened by the electrotonic spread of the NMDAR-mediated depolarization elicited in the dendrites. In contrast, we were unable to detect direct activation of NMDARs on axons, indicating an exclusive somatodendritic expression of functional NMDARs. In cerebellar stellate cells, dendritic NMDAR activation masquerades as a presynaptic phenomenon and may influence Ca(2+) -dependent forms of presynaptic plasticity and release.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Calcium / metabolism
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Calcium Channels / drug effects
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Calcium Channels / metabolism*
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cerebellar Cortex / metabolism*
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Cerebellar Cortex / ultrastructure
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Dendrites / drug effects
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Dendrites / metabolism*
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Dendrites / ultrastructure
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Excitatory Amino Acid Agonists / pharmacology
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Excitatory Postsynaptic Potentials / drug effects
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Excitatory Postsynaptic Potentials / physiology
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Glutamic Acid / metabolism
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Interneurons / drug effects
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Interneurons / metabolism*
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Interneurons / ultrastructure
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Ion Channel Gating / drug effects
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Ion Channel Gating / physiology
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Long-Term Synaptic Depression / drug effects
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Long-Term Synaptic Depression / physiology
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Microscopy, Confocal
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Organ Culture Techniques
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Patch-Clamp Techniques
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism*
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Presynaptic Terminals / ultrastructure
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Rats
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Calcium Channels
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Excitatory Amino Acid Agonists
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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Calcium