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Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction
Brett C Carter1, Craig E Jahr1
1Vollum Institute, Oregon Health &Science University, Portland, Oregon USA.
Nature Neuroscience
|July 12, 2016
Summary
Long-term depression (LTD) at cortical synapses requires NMDA receptors (NMDARs). This study reveals that postsynaptic NMDARs, not presynaptic ones, are essential for inducing LTD in young rodents.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Cortical Circuits
Background:
- Long-term depression (LTD) is a crucial form of synaptic plasticity.
- LTD at the cortical layer 4 (L4) to layer 2/3 (L2/3) synapse is NMDAR-dependent.
- Previous studies suggested presynaptic NMDAR involvement in young rodents.
Purpose of the Study:
- To investigate the precise localization of NMDARs required for LTD induction at the L4-L2/3 synapse.
- To determine whether presynaptic or postsynaptic NMDARs are critical for LTD in young rats and mice.
Main Methods:
- Two-photon laser scanning microscopy and glutamate uncaging to assess functional NMDARs in L4 axons.
- Genetic manipulation to delete postsynaptic or presynaptic NMDARs.
- Pharmacological analysis of NMDAR involvement.
Main Results:
- No evidence of functional NMDARs was found in L4 neuron presynaptic terminals.
- Genetic deletion of postsynaptic NMDARs abolished LTD induction.
- Presynaptic NMDAR deletion did not prevent LTD induction.
- The observed NMDAR requirement suggests a nonionic signaling mechanism.
Conclusions:
- Postsynaptic NMDARs, not presynaptic, are essential for LTD induction at the L4-L2/3 cortical synapse in young rodents.
- This finding challenges previous assumptions about presynaptic NMDAR roles in this specific circuit.
- The results highlight the importance of postsynaptic mechanisms in regulating synaptic plasticity.
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