PRESYNAPTIC CHANGES DURING MOSSY FIBER 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 plasticity(1-4). In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses(5,6), which express primarily an NMDA receptor-dependent form of LTP(7). In contrast, these studies(5,6) have suggested that messy fibre synapses activate primarily or exclusively alpha-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 receptors(8,9). Here we present physiological data demonstrating that messy fibres activate a substantial NMDA receptor synaptic component that expresses LTP. The presence of an NMDA receptor response allowed us to use the open-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of messy fibre LTP.