Aim: 

Synapsins (Syns) are synaptic vesicle phosphoproteins that play a role in synaptic transmission and plasticity by acting at multiple steps of exocytosis. Mutation of SYN gene results in an epileptic phenotype in mouse and man, implicating Syns in the control of network excitability.

Methods: 

We used microelectrode array and patch-clamp recordings to study spontaneous network activity and synaptic transmission respectively in cortical neurons from wild-type (WT), Syn I or Syn I/II/III knockout (KO) mice.

Results: 

The ablation of the SYN genes was associated with a highly increased spontaneous activity with more frequent and sustained bursts of action potentials. KO neuron revealed an increased burst duration and bursting rate. Such effect was partially maintained under treatment with bicuculline suggesting that both excitatory and inhibitory transmission were altered by Syn deletion. Patch-clamp recordings on cortical KO neurons revealed a reduction in the amplitude of evoked inhibitory postsynaptic currents (IPSCs) and an increase in the amplitude of EPSCs, attributable to opposite changes in the size of the readily releasable pool of synaptic vesicles. Inhibitory KO synapses showed unaltered paired-pulse ratio (PPR) and post-tetanic potentation (PTP), but a moderate increase of synaptic depression and a slow-down of recovery from depression. On the contrary excitatory synapses showed increased PPR and PTP, while a stronger synaptic depression and a slower recovery from depression was observed in Syn I/II/III KO hippocampal slices but not in Syn I KO cultured neurons.

Conclusion: 

These results show distinct effect of the lack of Syns on GABAergic and glutamatergic synapses providing an explanation for the high susceptibility of SynI and I/II/III KO mice to epileptic seizures.