title: Subconvulsant doses of pentylenetetrazol uncover the epileptic phenotype of cultured synapsin-deficient Helix serotonergic neurons in the absence of excitatory and inhibitory inputs.
abstract: Synapsins are a family of presynaptic proteins related to several processes of synaptic functioning. A variety of reports have linked mutations in synapsin genes with the development of epilepsy. Among the proposed mechanisms, a main one is based on the synapsin-mediated imbalance towards network hyperexcitability due to differential effects on neurotransmitter release in GABAergic and glutamatergic synapses. Along this line, a non-synaptic effect of synapsin depletion increasing neuronal excitability has recently been described in Helix neurons. To further investigate this issue, we examined the effect of synapsin knock-down on the development of pentylenetetrazol (PTZ)-induced epileptic-like activity using single neurons or isolated monosynaptic circuits reconstructed on microelectrode arrays (MEAs). Compared to control neurons, synapsin-silenced neurons showed a lower threshold for the development of epileptic-like activity and prolonged periods of activity, together with the occurrence of spontaneous firing after recurrent PTZ-induced epileptic-like activity. These findings highlight the crucial role of synapsin on neuronal excitability regulation in the absence of inhibitory or excitatory inputs.
authors.affiliation: Department of Neuroscience, Section of Physiology, University of Turin, Turin, Italy; Department of Physiology, School of Medicine, University of Costa Rica, San José, Costa Rica. Electronic address: oscar.brenes_g@ucr.ac.cr.
authors.forename: Oscar
authors.initials: O
authors.lastname: Brenes
authors.affiliation: Department of Drug Science, Lab of Cellular and Molecular Neuroscience, Turin, Italy; Nanostructured Interfaces and Surfaces Center, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carabelli
authors.affiliation: Department of Drug Science, Lab of Cellular and Molecular Neuroscience, Turin, Italy; Nanostructured Interfaces and Surfaces Center, Turin, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Gosso
authors.affiliation: School of Biology, University of Costa Rica, San José, Costa Rica.
authors.forename: Adarli
authors.initials: A
authors.lastname: Romero
authors.affiliation: Department of Drug Science, Lab of Cellular and Molecular Neuroscience, Turin, Italy; Nanostructured Interfaces and Surfaces Center, Turin, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Carbone
authors.affiliation: Department of Neuroscience, Section of Physiology, University of Turin, Turin, Italy; National Institute of Neuroscience, Turin, Italy.
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Montarolo
authors.affiliation: Department of Neuroscience, Section of Physiology, University of Turin, Turin, Italy; National Institute of Neuroscience, Turin, Italy.
authors.forename: Mirella
authors.initials: M
authors.lastname: Ghirardi
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003292:Convulsants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006372:Helix, Snails; D008839:Microelectrodes; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000494:pharmacology*; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D016704:Synapsins / Q000172:deficiency*
chemical_list: D003292:Convulsants; D016704:Synapsins; D010433:Pentylenetetrazole
keywords: Convulsants; Helix snail; Invertebrate neurons; Pentylenetetrazol (PTZ); Synapsin