Opposite changes in glutamatergic and GABAergic transmission underlie the diffuse hyperexcitability of synapsin I-deficient cortical networks.
Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play a role in synaptic transmission and plasticity. Mutation of the SYN1 gene results in an epileptic phenotype in mouse and man, implicating SynI in the control of network excitability. We used microelectrode array and patch-clamp recordings to study network activity in primary cortical neurons from wild-type (WT) or SynI knockout (KO) mice. SYN1 deletion was associated with increased spontaneous and evoked activities, with more frequent and sustained bursts of action potentials and a high degree of synchronization. Blockade of GABA(A) (gamma-aminobutyric acid(A)) receptors with bicuculline attenuated, but did not completely abolish, the differences between WT and SynI KO networks in both spontaneous and evoked activities. Patch-clamp recordings on cortical autaptic neurons revealed a reduced amplitude of evoked inhibitory postsynaptic currents (PSCs) and a concomitantly increased amplitude of evoked excitatory PSCs in SynI KO neurons, in the absence of changes in miniature PSCs. Cumulative amplitude analysis revealed that these effects were attributable to opposite changes in the size of the readily releasable pool of SVs. The results indicate distinct roles of SynI in GABAergic and glutamatergic neurons and provide an explanation for the high susceptibility of SynI KO mice to epileptic seizures.
Chiappalone
Michela
M
Department of Neuroscience and Brain Technologies, The Italian Institute of Technology, Genova, Italy.
Casagrande
Silvia
S
Tedesco
Mariateresa
M
Valtorta
Flavia
F
Baldelli
Pietro
P
Martinoia
Sergio
S
Benfenati
Fabio
F
D000200:Action Potentials; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D016704:Synapsins; D005680:gamma-Aminobutyric Acid