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 plasticity. In the CA1 region of the hippocampus, anatomical studies have revealed large numbers of NMDA (N-methyl-D-aspartate) receptor sites at excitatory synapses, which express primarily an NMDA receptor-dependent form of LTP. In contrast, these studies have suggested that mossy 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. 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 open-channel NMDA receptor antagonist MK-801 to establish directly that the probability of transmitter release is enhanced during the expression of mossy fibre LTP.
Weisskopf
M G
MG
Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143-0450, USA.
Nicoll
R A
RA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008564:Membrane Potentials; D009412:Nerve Fibers / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism
D018377:Neurotransmitter Agents; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione