Abstract

The search for mechanisms in neocortex that change synaptic efficacy and produce associative learning through activity-dependent processes has focused on the role of glutamate receptors of the N-methyl- d-aspartate (NMDA) type. NMDA receptor activation is necessary for the induction of long-term potentiation (LTP) in hippocampus 12 and in neocortex 2. The effect of NMDA receptor activation is modulated in several ways, including Mg 2+ block of the NMDA-dependent channel which prevents Ca 2+ entry until neurons become partially depolarized 25,32. We report that when NMDA receptor activation is facilitated by lowering the extracellular [Mg 2+] in the bathing medium, a low-frequency train presented in layer VI induces potentiated responses throughout a wide horizontal extent of layer II/III in neocortical slices. The response amplitudes potentiated by 34–200% over baseline values depending on the intensity of the repetitive conditioning stimulus and the distance of the recording site from the stimulus. At the same time that pre-existing evoked responses were potentiated, horizontal spread of activity in layer II/III was facilitated resulting in responses appearing at sites more than 1 mm from the stimulus. This enhanced transmission of responses persisted for >2 h, and its induction was prevented by s spread of activity can be increased by altering the conditions of the stimulus presentation. We conclude that the mechanisms supporting LTP could determine the area of neocortex that is activated by a sensory input.

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