Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A-deficient but not SV2B-deficient mice

Venkatesan, Kumar and Alix, Philippe and Marquet, Alice and Doupagne, Melissa and Niespodziany, Isabelle and Rogister, Bernard and Seutin, Vincent (2012) Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A-deficient but not SV2B-deficient mice. Journal of Neuroscience Research, 90 (12). pp. 2317-2327. ISSN 03604012

[img] PDF
Altered Balance Between Excitatory and.pdf

Download (622kB)
Official URL: http://dx.doi.org/10.1002/jnr.23111

Abstract

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 GABAA 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 potentialand Ca21-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

Item Type: Article
Subjects: Pharmaceutical Sciences
Divisions: College of Pharmacy > Pharmaceutical Sciences
Depositing User: Dr KUMAR Venkatesan
Date Deposited: 31 May 2017 10:57
Last Modified: 31 May 2017 10:57
URI: http://eprints.kku.edu.sa/id/eprint/771

Actions (login required)

View Item View Item