Abstract
In the developing brain, many glutamate synapses have been found to transmit only NMDA receptor-mediated signaling, that is, they are AMPA-silent. This result has been taken to suggest that glutamate synapses are initially AMPA-silent when they are formed, and that AMPA signaling is acquired through activity-dependent synaptic plasticity. The present study on CA3-CA1 synapses in the hippocampus of the neonatal rat suggests that AMPA-silent synapses are created through a form of activity-dependent silencing of AMPA signaling. We found that AMPA signaling, but not NMDA signaling, could be very rapidly silenced by presynaptic electrical stimulation at frequencies commonly used to probe synaptic function (0.05-1 Hz). Although this AMPA silencing required a rise in postsynaptic Ca(2+), it did not require activation of NMDA receptors, metabotropic glutamate receptors or voltage-gated calcium channels. The AMPA silencing, possibly explained by a removal of postsynaptic AMPA receptors, could subsequently be reversed by paired presynaptic and postsynaptic activity.
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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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Cell Differentiation / drug effects
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Cell Differentiation / physiology*
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Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Electric Stimulation
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Antagonists
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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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Hippocampus / cytology
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Hippocampus / growth & development*
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Hippocampus / metabolism
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In Vitro Techniques
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Rats
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Rats, Wistar
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Receptors, AMPA / drug effects
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Receptors, AMPA / metabolism*
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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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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synapses / drug effects
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Synapses / metabolism*
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Synaptic Vesicles / drug effects
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Synaptic Vesicles / metabolism
Substances
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Enzyme Inhibitors
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Excitatory Amino Acid Antagonists
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Glutamic Acid
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Cyclic AMP-Dependent Protein Kinases