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The Journal of Neuroscience, July 18, 2007, 27(29):7740-7750; doi:10.1523/JNEUROSCI.1604-07.2007

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Cellular/Molecular
Presynaptic Contributions of Chordin to Hippocampal Plasticity and Spatial Learning

Mu Sun,^1,2 Mark J. Thomas,^3,4 Rachel Herder,² M. Lisa Bofenkamp,^1,2 Scott B. Selleck,^2,5 and Michael B. O'Connor^1,2

¹Howard Hughes Medical Institute and Departments of ²Genetics, Cell Biology, and Development, ³Neuroscience, ⁴Psychology, and ⁵Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455

Correspondence should be addressed to Michael B. O'Connor, Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, University of Minnesota, Minneapolis, MN 55455. Email: moconnor{at}mail.med.umn.edu

Recently, several evolutionary conserved signaling pathways that play prominent roles in regulating early neurodevelopment have been found to regulate synaptic remodeling in the adult. To test whether adult neuronal expression of bone morphogenic protein (BMP) signaling components also plays a postnatal role in regulating neuronal plasticity, we modulated BMP signaling in mice both in vivo and in vitro by genetic removal of the BMP inhibitor chordin or by perfusing recombinant BMP signaling pathway components onto acute hippocampal slices. Chordin null mice exhibited a significant increase in presynaptic transmitter release from hippocampal neurons, resulting in enhanced paired-pulse facilitation and long-term potentiation. These mice also showed a decreased acquisition time in a water maze test along with less exploratory activity during Y-maze and open-field tests. Perfusion of BMP ligands onto hippocampal slices replicated the presynaptic phenotype of chordin null slices, but bath application of Noggin, another antagonist of BMP signaling pathway, significantly decrease the frequency of miniature EPSCs. These results demonstrate that the BMP signaling pathway contributes to synaptic plasticity and learning likely through a presynaptic mechanism.

Key words: BMP; chordin; hippocampus; synaptic plasticity; learning and memory; neurotransmission

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Received April 10, 2007; revised June 2, 2007; accepted June 6, 2007.

Correspondence should be addressed to Michael B. O'Connor, Department of Genetics, Cell Biology, and Development, 6-160 Jackson Hall, University of Minnesota, Minneapolis, MN 55455. Email: moconnor{at}mail.med.umn.edu

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