Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Animals
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Animals, Newborn
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Blotting, Western / methods
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Disks Large Homolog 4 Protein
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Dose-Response Relationship, Drug
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Electroencephalography
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Excitatory Postsynaptic Potentials
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Hippocampus / cytology*
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Hippocampus / drug effects
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Hippocampus / physiology
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Humans
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In Situ Hybridization / methods
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In Vitro Techniques
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / deficiency
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Membrane Proteins / metabolism
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Membrane Proteins / pharmacology
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Mice
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Mice, Knockout / physiology
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / pharmacology
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Neuropilin-1 / metabolism
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Neuropilin-2 / metabolism
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Patch-Clamp Techniques / methods
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Prosencephalon / cytology
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Rats
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Reaction Time / drug effects
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Receptors, AMPA / metabolism
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Semaphorins / physiology*
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Subcellular Fractions / drug effects
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Subcellular Fractions / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology*
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Synaptophysin / metabolism
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Time Factors
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, rat
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Neuropilin-2
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Receptors, AMPA
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Sema3f protein, mouse
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Semaphorins
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Synaptophysin
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Neuropilin-1
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glutamate receptor ionotropic, AMPA 2