[en] Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms, SV2A, SV2B, and SV2C. SV2A knockout (KO) mice and SV2A/SV2B double KO (DKO) mice, but not SV2B KO animals, start to experience severe seizures and weight loss 7 days after birth and die at about postnatal day (P)14-P23. Because excitatory and inhibitory inputs play a major role in controlling neuronal excitability in the hippocampus, we examined the effects of SV2A and/or SV2B deletions on glutamatergic and GABA(A) neurotransmission in hippocampal CA1 pyramidal neurons. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, mEPSCs, sIPSCs, and mIPSCs, respectively) were recorded using the whole-cell patch-clamp technique in slices from P6-P14 mice. The frequency of sEPSCs was increased in SV2A KO and SV2A/SV2B DKO mice, but their amplitude was unchanged. Such changes were not observed in SV2B KOs. On the contrary, the frequency and amplitude of sIPSCs were decreased in SV2A KO and SV2A/SV2B DKO mice but not in SV2B KO animals, as reported previously for the CA3 region. Kinetic parameters of sIPSCs and sEPSCs were unchanged. Importantly, no changes were observed in any genotype when examining mEPSCs and mIPSCs. We conclude that action potential- and Ca(2+) -dependent glutamatergic and GABAergic synaptic transmission are differentially altered in the hippocampus of SV2A-deficient mice, whereas the mechanism of exocytosis itself is not changed. The altered balance between these major excitatory and inhibitory inputs is probably a contributing factor to seizures in SV2A KO and SV2A/SV2B DKO mice. (c) 2012 Wiley Periodicals, Inc.
Disciplines :
Neurosciences & behavior
Author, co-author :
Venkatesan, Kumar
Alix, Philippe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Marquet, Alice
Doupagne, Melissa
Niespodziany, Isabelle
ROGISTER, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Neurologie Sart Tilman
Seutin, Vincent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Language :
English
Title :
Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A-deficient but not SV2B-deficient mice.
Publication date :
2012
Journal title :
Journal of Neuroscience Research
ISSN :
0360-4012
eISSN :
1097-4547
Publisher :
John Wiley & Sons, Hoboken, United States - New York
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