Presynaptic changes during mossy fibre LTP revealed by NMDA receptor-mediated synaptic responses

ACTIVITY-DEPENDENT changes in synaptic strength are important for learning and memory. Long-term potentiation (LTP) of glutamatergic excitatory synapses following brief repetitive stimulation provides a compelling cellular model for such plasticity1á¤-4. In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses5,6, which express primarily an NMDA receptor-dependent form of LTP7. In contrast, these studies5,6 have suggested that mossy fibre synapses activate primarily or exclusively α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and, indeed, these synapses express a form of LTP that is entirely independent of NMDA receptors8,9. Here we present physiological data demonstrating that mossy fibres activate a substantial NMDA receptor synaptic component that expresses LTP. The presence of an NMDA receptor response allowed us to use the pen-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of mossy fibre LTP.

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