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Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation


Hippocampal mossy fiber synapses show an unusual form of long-term potentiation (LTP) that is independent of NMDA receptor activation and is expressed presynaptically. Using receptor antagonists, as well as receptor knockout mice, we found that presynaptic kainate receptors facilitate the induction of mossy fiber long-term potentiation (LTP), although they are not required for this form of LTP. Most importantly, these receptors impart an associativity to mossy fiber LTP such that activity in neighboring mossy fiber synapses, or even associational/commissural synapses, influences the threshold for inducing mossy fiber LTP. Such a mechanism greatly increases the computational power of this form of plasticity.

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Figure 1: KAR blockade increases the threshold for LTP induction.
Figure 2: KAR blockade shifts the threshold for LTP induction.
Figure 3: KARs modulate the threshold for LTP induction as monitored with field potential recordings.
Figure 4: Application of K+ converts a subthreshold tetanus into an effective one.
Figure 5: Application of K+ or strong tetani rescue mossy fiber LTP in the GluR6 knockout mouse.
Figure 6: KARs impart a cooperativity/associativity to mossy fiber LTP.
Figure 7: The cooperativity/associativity of mossy fiber LTP is mediated by KARs.


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We thank M. Frerking for his helpful discussions in this study. D.S. is supported by grants from the Deutsche Forschungsgemeinschaft (Emmy-Noether-Programm, SFB618) and J.M. by a Wellcome Trust Travelling Fellowship. R.A.N. is a member of the Keck Center for Integrative Neuroscience and the Silvio Conte Center for Neuroscience Research and is supported by grants from the US National Institutes of Health and the Bristol-Myers Squibb Co. We thank S. Heinemann for the GluR5 and GluR6 knockout mice and S. Karimzadegan for technical assistance.

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Correspondence to Roger A Nicoll.

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Schmitz, D., Mellor, J., Breustedt, J. et al. Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation. Nat Neurosci 6, 1058–1063 (2003).

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