The synapsin domain E accelerates the exoendocytotic cycle of synaptic vesicles in cerebellar Purkinje cells.
Synapsins are synaptic-vesicle-associated phosphoproteins implicated in the regulation of neurotransmitter release and excitability of neuronal networks. Mutation of synapsin genes in mouse and human causes epilepsy. To understand the role of the highly conserved synapsin domain E in the dynamics of release from mammalian inhibitory neurons, we generated mice that selectively overexpress the most conserved part of this domain in cerebellar Purkinje cells. At Purkinje-cell-nuclear-neuron synapses, transgenic mice were more resistant to depression induced by short or prolonged high-frequency stimulations. The increased synaptic performance was accompanied by accelerated release kinetics and shorter synaptic delay. Despite a marked decrease in the total number of synaptic vesicles, vesicles at the active zone were preserved or slightly increased. The data indicate that synapsin domain E increases synaptic efficiency by accelerating both the kinetics of exocytosis and the rate of synaptic vesicle cycling and decreasing depression at the inhibitory Purkinje-cell-nuclear-neuron synapse. These effects may increase the sensitivity of postsynaptic neurons to inhibition and thereby contribute to the inhibitory control of network activity.
Fassio
Anna
A
Center of Neuroscience and Neuroengineering, Department of Experimental Medicine, University of Genoa, Italy.
Merlo
Daniela
D
Mapelli
Jonathan
J
Menegon
Andrea
A
Corradi
Anna
A
Mete
Maurizio
M
Zappettini
Simona
S
Bonanno
Giambattista
G
Valtorta
Flavia
F
D'Angelo
Egidio
E
Benfenati
Fabio
F
D000595:Amino Acid Sequence; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001665:Binding Sites / Q000235:genetics; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D016704:Synapsins / Q000235:genetics / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D020033:Protein Isoforms; D016704:Synapsins; D005680:gamma-Aminobutyric Acid; D015759:Ionomycin