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Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons


The hippocampus is necessary for the acquisition and retrieval of declarative memories1,2. The best-characterized sensory input to the hippocampus is the perforant path projection from layer II of entorhinal cortex (EC) to the dentate gyrus3,4. Signals are then processed sequentially in the hippocampal CA fields before returning to the cortex via CA1 pyramidal neuron spikes. There is another EC input—the temporoammonic (TA) pathway—consisting of axons from layer III EC neurons that make synaptic contacts on the distal dendrites of CA1 neurons3,5,6. Here we show that this pathway modulates both the plasticity and the output of the rat hippocampal formation. Bursts of TA activity can, depending on their timing, either increase or decrease the probability of Schaffer-collateral (SC)-evoked CA1 spikes. TA bursts can also significantly reduce the magnitude of synaptic potentiation at SC–CA1 synapses. The TA–CA1 synapse itself exhibits both long-term depression (LTD) and long-term potentiation (LTP). This capacity for bi-directional plasticity can, in turn, regulate the TA modulation of CA1 activity: LTP or LTD of the TA pathway either enhances or diminishes the gating of CA1 spikes and plasticity inhibition, respectively.

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Figure 1: Enhancement and inhibition of SC-driven spikes by stimulation of TA.
Figure 2: Interference with plasticity by stimulation of TA.
Figure 3: TA–CA1 synapses exhibit NMDA-receptor-dependent LTP.
Figure 4: Modulation of spike blocking and spike enhancement by TA-LTP and LTD.
Figure 5: Modulation of interference with plasticity by TA-LTP and LTD.


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We thank G. Laurent for critial reading of the manuscript. This work was supported by Fundacao para a Ciencia e Tecnologia (FCT)—Portugal and the Howard Hughes Medical Institute.

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Correspondence to Erin M. Schuman.

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Remondes, M., Schuman, E. Direct cortical input modulates plasticity and spiking in CA1 pyramidal neurons. Nature 416, 736–740 (2002).

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