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Hebbian LTP in feed-forward inhibitory interneurons and the temporal fidelity of input discrimination

Nature Neuroscience volume 8, pages 916–924 (2005)Cite this article

Abstract

Cortical information processing requires a delicate balance of excitatory and inhibitory signaling. How is this balance preserved during hippocampal memory encoding, which involves NMDA receptor–dependent long term potentiation (LTP)? This form of LTP occurs at synapses between pyramidal neurons but has not been detected in feed-forward inhibitory interneurons. We show that paired pre- and postsynaptic activity evokes pathway-specific LTP in half of rat stratum radiatum interneurons if cytoplasmic integrity is preserved. LTP occurs in aspiny feed-forward interneurons and propagates to pyramidal neurons as an enhancement of disynaptic inhibition. We also show that when LTP is restricted to synapses on pyramidal neurons, the temporal fidelity of synaptic integration and action potential generation in pyramidal cells is compromised. However, when LTP also occurs at synapses on feed-forward interneurons, temporal fidelity is preserved. We propose that Hebbian LTP at synapses driving disynaptic inhibition is necessary to maintain information processing without degradation during memory encoding.

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Figure 1: Hebbian LTP in CA1 stratum radiatum interneurons.
Figure 2: Induction of LTP requires activation of NMDARs and cellular integrity.
Figure 3: Hebbian plasticity occurs in feed-forward interneurons.
Figure 4: LTP does not spread to other interneurons.
Figure 5: Hebbian LTP can be elicited by synaptic depolarization and propagates to pyramidal neurons.
Figure 6: Measurement of the time window for action potential generation in the face of asynchronous afferent stimulation.
Figure 7: LTP in pyramidal cells compromises the fidelity of coincidence detection in pyramidal cells.
Figure 8: Tetanic stimulation-evoked LTP, designed to potentiate not only synapses on pyramidal neurons but also on feed-forward interneurons, preserves the fidelity of coincidence detection.

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Acknowledgements

We thank D.A. Rusakov, R.A. Silver, M.C. Walker and R.W. Tsien for comments. Supported by the Wellcome Trust, the Academy of Finland and the UK Medical Research Council.

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Authors and Affiliations

  1. Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK

    Karri Lamsa, Joost H Heeroma & Dimitri M Kullmann

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Correspondence to Dimitri M Kullmann.

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Supplementary information

Supplementary Fig. 1

LTP induction protocols in CA1 stratum radiatum interneurons. (PDF 409 kb)

Supplementary Fig. 2

Procedure used to fill interneurons for post hoc morphological characterization. (PDF 439 kb)

Supplementary Fig. 3

Electrophysiological parameters in interneurons exhibiting LTP or no LTP. (PDF 207 kb)

Supplementary Fig. 4

Pairing-evoked LTP evoked in the presence of picrotoxin to block GABAA receptors has no effect on the temporal fidelity of coincidence detection. (PDF 959 kb)

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Lamsa, K., Heeroma, J. & Kullmann, D. Hebbian LTP in feed-forward inhibitory interneurons and the temporal fidelity of input discrimination. Nat Neurosci 8, 916–924 (2005). https://doi.org/10.1038/nn1486

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