Secreted semaphorins modulate synaptic transmission in the adult hippocampus.
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.
Sahay
Amar
A
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Kim
Chong-Hyun
CH
Sepkuty
Jehuda P
JP
Cho
Edward
E
Huganir
Richard L
RL
Ginty
David D
DD
Kolodkin
Alex L
AL
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000494:pharmacology; D039942:Neuropilin-1 / Q000378:metabolism; D039943:Neuropilin-2 / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D016548:Prosencephalon / Q000166:cytology; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D018091:Receptors, AMPA / Q000378:metabolism; D039961:Semaphorins / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; D018091:Receptors, AMPA; C491229:Sema3f protein, mouse; D039961:Semaphorins; D016708:Synaptophysin; D039942:Neuropilin-1; C104722:glutamate receptor ionotropic, AMPA 2