Subconvulsant doses of pentylenetetrazol uncover the epileptic phenotype of cultured synapsin-deficient Helix serotonergic neurons in the absence of excitatory and inhibitory inputs
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Date
2016-09-06Author
Brenes García, Oscar Gerardo
Caravelli, Valentina
Gosso, Sara
Romero Vásquez, Adarli
Carbone, Emilio
Montarolo, Pier Giorgio
Ghirardi, Mirella
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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.