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Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism

Nature Neuroscience volume 2, pages 625–633 (1999) Cite this article

Abstract

We investigated long-term potentiation (LTP) at mossy fiber synapses on CA3 pyramidal neurons in the hippocampus. Using Ca2+ imaging techniques, we show here that when postsynaptic Ca2+ was sufficiently buffered so that [Ca2+]i did not rise during synaptic stimulation, the induction of mossy fiber LTP was prevented. In addition, induction of mossy fiber LTP was suppressed by postsynaptic injection of a peptide inhibitor of cAMP-dependent protein kinase. Finally, when ionotropic glutamate receptors were blocked, LTP depended on the postsynaptic release of Ca2+ from internal stores triggered by activation of metabotropic glutamate receptors. These results support the conclusion that mossy fiber LTP and LTP at other hippocampal synapses share a common induction mechanism involving an initial rise in postsynaptic [Ca2+].

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Figure 1: Contrasting properties of mossy fiber (mf) and commissural/associational (C/A) evoked synaptic responses.
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Figure 2: Mossy fiber LTP induced by three different stimulation protocols.
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Figure 3: Effects of postsynaptic BAPTA on the induction of mossy fiber LTP with B-HFS and L-HFS.
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Figure 4: Ca2+ fluorescence imaging during B-HFS and L-HFS.
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Figure 5: High BAPTA blocks Ca2+ signals and LTP.
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Figure 6: Suppressing synaptic transmission alone does not prevent mossy fiber LTP.
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Figure 7: Ca2+ release from internal stores when fast synaptic transmission is blocked.
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Figure 8: Postsynaptic inhibition of PKA blocked mossy fiber LTP.
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Acknowledgements

We thank Tom Brown, Jeff Magee, Nick Poolos and Bob Zucker for comments on the manuscript and Rick Gray for help through various stages of this project. We also thank Nathan Urban for help with L-HFS LTP, David Sweatt for advice on the PKA inhibitor experiments and Rob Gereau for advice on the mGluR experiments. This work was supported by NIH grants MH11390 (MFY) and MH44754 and MH48432 (D.J.), HFSP and the Hankamer Foundation.

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  1. Division of Neuroscience, Baylor College of Medicine One Baylor Plaza, Houston, 77030, Texas, USA

    Mark F. Yeckel, Ajay Kapur & Daniel Johnston

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  1. Mark F. Yeckel
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Correspondence to Daniel Johnston.

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Yeckel, M., Kapur, A. & Johnston, D. Multiple forms of LTP in hippocampal CA3 neurons use a common postsynaptic mechanism. Nat Neurosci 2, 625–633 (1999). https://doi.org/10.1038/10180

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