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The Journal of Neuroscience, April 6, 2005, 25(14):3613-3620; doi:10.1523/JNEUROSCI.5255-04.2005

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Cellular/Molecular
Secreted Semaphorins Modulate Synaptic Transmission in the Adult Hippocampus

Amar Sahay,^1 4* Chong-Hyun Kim,^1,3 * Jehuda P. Sepkuty,² Edward Cho,² Richard L. Huganir,^1,3 David D. Ginty,^1,3 and Alex L. Kolodkin¹

Departments of ¹Neuroscience and ²Neurology and ³Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

Modulation of synaptic activity is critical for neural circuit function and behavior. The semaphorins are a large, phylogenetically conserved protein family with important roles in neural development. However, semaphorin function in the adult brain has yet to be determined. Here, we show that the coreceptors for secreted semaphorins, the neuropilins, are found at synapses and localize to molecular layers of the adult mouse hippocampus and accessory olfactory cortex. Moreover, application of the secreted semaphorin Sema3F to acute hippocampal slices modulates both the frequency and amplitude of miniature EPSCs in granule cells of the dentate gyrus and pyramidal neurons of CA1. Finally, we show that mice lacking Sema3F are prone to seizures. These results suggest a novel role for semaphorins as synaptic modulators and illustrate the diverse repertoire of these guidance cues in both the formation and function of neural circuits.

Key words: semaphorins; synaptic plasticity; neuropilins; hippocampus; AMPA receptors; seizures

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Received Dec 23, 2004; revised February 21, 2005; accepted February 22, 2005.

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