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Science 315 (5816): 1262-1266

Copyright © 2007 by the American Association for the Advancement of Science

Anti-Hebbian Long-Term Potentiation in the Hippocampal Feedback Inhibitory Circuit

Karri P. Lamsa,1 Joost H. Heeroma,1 Peter Somogyi,2 Dmitri A. Rusakov,1 Dimitri M. Kullmann1*

Abstract: Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity.

1 Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK.
2 Anatomical Neuropharmacology Unit, Medical Research Council, Oxford University, Mansfield Road, Oxford OXI 3HT, UK.

* To whom correspondence should be addressed. E-mail: d.kullmann{at}

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