Long-term potentiation in frontal cortex: Role of NMDA-modulated polysynaptic excitatory pathways

The present study examined the role of N-methyl-D-aspartic acid
(NMDA) receptors in synaptic plasticity in regular-spiking cells of
rat frontal cortex. Intracortical stimulation, at levels
subthreshold for elicitation of action potentials, evoked a late
excitatory postsynaptic potential (EPSP) in layer II III neurons
that was sensitive to the selective NMDA antagonist
-2-amino-5-phosphonovaleric acid (APV). This late EPSP showed
marked short-term frequency-dependent depression, suggesting that
it is polysynaptic in origin. Polysynaptic late EPSPs were
selectively enhanced following high-frequency stimulation. This
sustained increase in synaptic efficacy, or long-term potentiation,
was expressed in regular spiking cells and appeared to result from
activation of NMDA receptors on excitatory interneurons. These data
demonstrate the existence of an NMDA-modulated polysynaptic circuit
in the neocortex which displays several types of use-dependent
plasticity.