Aim: 

Spike timing-dependent plasticity (STDP) is a strong candidate synaptic mechanism involved in cortical development and map plasticity. In STDP, the temporal order and precise timing of pre- and postsynaptic action potentials (spikes) determine the direction and magnitude of synaptic change. Both timing-dependent long-term potentiation (t-LTP) and timing-dependent long-term depression (t-LTD) depend on NMDA receptors. How the same type of receptor can be involved in opposite changes in synaptic efficacy is not well understood. Whereas it is established that postsynaptic NMDA receptors are necessary for t-LTP, we investigated here whether presynaptic NMDA receptors are necessary for timing-dependent LTD and LTP in layer (L) 4-to-L2/3 excitatory synapses in mouse barrel cortex.

Methods: 

We used paired whole-cell recordings of synaptically-connected L4 and L2/3 cells.

Results: 

In five pairs, a pre-before-post pairing protocol was applied with 1 mM MK-801 in the presynaptic pipette. Robust t-LTP was induced (1545%, n=5; p<0.01, t-test), of similar magnitude to that seen with extracellular stimulation (1539%, n=5), suggesting that presynaptic NMDA receptors are not neccessary for induction of t-LTP. In contrast, t-LTD was completely blocked when MK-801 was included in the presynaptic pipette (1046%, n=6), whilst in pairs of cells without MK-801 this protocol induced robust t-LTD (766%, n=6; p<0.01, t-test), indicating that presynaptic NMDA receptors are necessary for t-LTD.

Conclusion: 

The different sites of NMDA receptors necessary for induction of t-LTP and t-LTD may have important consequences for the computational operation of cortical microcircuits and map plasticity.