Spike timing-dependent long-term depression requires presynaptic NMDA receptors

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Molecular Neurobiology

Background:

• N-methyl-D-aspartate (NMDA) receptors are crucial for synaptic plasticity.
• The exact localization of NMDA receptors in presynaptic versus postsynaptic compartments for distinct plasticity forms remains unclear.

Purpose of the Study:

• To determine the precise cellular location (presynaptic or postsynaptic) of NMDA receptors involved in synaptic potentiation and depression.
• To elucidate the differential roles of pre- and postsynaptic NMDA receptors in modulating synaptic strength.

Main Methods:

• Paired recordings were performed in synaptically connected layer 4 and layer 2/3 neurons in the mouse barrel cortex.
• The NMDA receptor antagonist MK-801 was selectively loaded into either presynaptic or postsynaptic neurons to assess its impact on synaptic plasticity.

Main Results:

• Synaptic potentiation was impaired when postsynaptic NMDA receptors were blocked, but unaffected by presynaptic blockade.
• Synaptic depression was impaired when presynaptic NMDA receptors were blocked, but unaffected by postsynaptic blockade.

Conclusions:

• Postsynaptic NMDA receptors are essential for synaptic potentiation.
• Presynaptic NMDA receptors are essential for synaptic depression.
• These findings reveal a compartmentalized role for NMDA receptors in distinct forms of synaptic plasticity within the barrel cortex.