NMDA receptor-dependent metaplasticity at hippocampal mossy fiber synapses

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Hippocampal Circuitry

Background:

• Mossy fiber synapses in the hippocampus typically lack NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA excitatory postsynaptic currents (EPSCs).
• This absence is potentially due to a lower NMDAR expression at these specific synapses compared to other glutamatergic connections.

Purpose of the Study:

• To investigate the plasticity rules governing mossy fiber-CA3 synapses in mouse hippocampal slices.
• To determine if LTP selective for NMDARs influences the capacity for NMDAR-dependent LTP of AMPA EPSCs at these synapses.

Main Methods:

• Electrophysiological recordings in acute mouse hippocampal slices.
• Induction of LTP specifically targeting NMDARs at mossy fiber synapses.
• Measurement of subsequent changes in AMPA EPSCs to assess plasticity.

Main Results:

• Mossy fiber synapses, which normally do not exhibit NMDAR-dependent LTP of AMPA EPSCs, were found to become competent for this form of plasticity.
• This competence was achieved following the induction of LTP selective for NMDARs.
• NMDAR-LTP acted as a metaplastic switch, altering the synapse's ability to undergo further plasticity.

Conclusions:

• LTP of NMDARs can reconfigure mossy fiber synapses.
• This reconfiguration enables the generation of NMDAR-dependent LTP of AMPA EPSCs, a plasticity previously thought to be absent.
• These findings reveal a novel metaplastic mechanism in hippocampal circuitry.