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J Neurophysiol. 1997 Aug;78(2):1155-60.

Reversal of LTP in the hippocampal afferent fiber system to the prefrontal cortex in vivo with low-frequency patterns of stimulation that do not produce LTD.

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Laboratoire de Neurobiologie de l'Apprentissage et de la Mémoire, Centre National de la Recherche Scientifique URA 1491, Université Paris Sud, Orsay, France.


We examined the efficacy of several patterns of low-frequency stimulation for producing long-term depression (LTD) or depotentiation in the hippocampal fiber pathway to the prefrontal cortex in the anesthetized rat. Field potentials elicited by stimulation of the CA1/subicular region of the ventral hippocampus were recorded in the prelimbic area of the prefrontal cortex. We found no evidence that low-frequency trains (0.5-1 Hz), consisting of either single pulses, paired pulses (35-ms interpulse interval), or two-pulse bursts (5-ms interval), produce LTD in the prefrontal cortex. In contrast, all three stimulus protocols were found to induce a small-amplitude, persistent potentiation of the amplitude of the negative wave of the field response recorded in the prefrontal cortex. We also examined the ability of patterns of low-frequency stimulation to produce depotentiation of previously established long-term potentiation (LTP). Although low-frequency stimulation with single pulses or paired pulses was ineffective, we found that the two-pulse burst protocol selectively produced a rapid reversal of LTP in the hippocampo-prefrontal cortex pathway. Depotentiation is reversible and can be induced >2 h after the induction of LTP. Repeated trains failed to decrease the prefrontal cortex response below the original, unpotentiated level. These findings demonstrate the existence of a depotentiation mechanism that is capable of exerting powerful control over ongoing or recently induced synaptic plasticity in hippocampocortical connections in vivo.

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