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Updated: Aug 12, 2026

Presynaptically Silent Synapses Studied with Light Microscopy
Published on: January 4, 2010
Evidence for silent synapses: implications for the expression of LTP
J T Isaac1, R A Nicoll, R C Malenka
1Department of Psychiatry, University of California, San Francisco 94143, USA.
Silent synapses in the hippocampus can become functional after long-term potentiation (LTP) induction. This study shows that NMDA receptor (NMDAR) activation leads to AMPA receptor (AMPAR) insertion, converting silent synapses to active ones.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Neurobiology
Background:
- Some excitatory synapses on hippocampal CA1 pyramidal cells express NMDA receptors (NMDARs) but lack functional AMPA receptors (AMPARs), rendering them silent at resting membrane potential.
- These silent synapses are crucial for synaptic plasticity and memory formation, but their precise role and activation mechanisms remain under investigation.
Purpose of the Study:
- To investigate the functional conversion of silent excitatory synapses into active ones in hippocampal CA1 pyramidal cells.
- To determine the role of NMDA receptors (NMDARs) and AMPA receptors (AMPARs) in this synaptic modification process.
- To explore the potential contribution of silent synapse modification to long-term potentiation (LTP).
Main Methods:
- Electrophysiological recordings in hippocampal CA1 pyramidal cells.
- Stimulation of synapses at different holding potentials (-60 mV and +30 to +60 mV).
- Application of NMDAR antagonist D-APV and LTP induction protocols.
Main Results:
- Synapses yielding no detectable excitatory postsynaptic currents (EPSCs) at -60 mV were identified.
- EPSCs were elicited at positive potentials, blocked by D-APV, confirming NMDAR involvement.
- LTP induction converted silent synapses to functional ones, with AMPAR-mediated EPSCs appearing and persisting.
- This conversion was blocked by D-APV, indicating NMDAR-dependent AMPAR insertion.
Conclusions:
- Long-term potentiation (LTP) likely involves the modification of AMPA receptors (AMPARs) at previously silent synapses.
- The conversion of silent synapses to functional ones is mediated by NMDAR activation and subsequent AMPAR insertion.
- This mechanism provides a cellular basis for LTP and may explain experimental findings previously attributed to presynaptic changes.
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