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

• Published in: Nature (London) 1995-07, Vol.376 (6537), p.256-259
• Main Authors: Weisskopf, Marc G., Nicoll, Roger A.
• Format: Article
• Language: English
• Subjects: 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Animals; Biological and medical sciences; Brain; Cellular biology; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dizocilpine Maleate - pharmacology; Fibers; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Hippocampus - physiology; Humanities and Social Sciences; In Vitro Techniques; Learning; letter; Long-Term Potentiation - physiology; Membrane Potentials; Memory; multidisciplinary; Nerve Fibers - physiology; Neurons, Afferent - physiology; Neurotransmitter Agents - metabolism; Physiology; Pyramidal Cells - physiology; Receptors, AMPA - antagonists & inhibitors; Receptors, AMPA - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Science; Science (multidisciplinary); Synapses - physiology; Synaptic Membranes - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/376256a0

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 1á¤-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 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 receptors 8,9 . 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.