Synapsin-dependent development of glutamatergic synaptic vesicles and presynaptic plasticity in postnatal mouse brain.
Inactivation of the genes encoding the neuronal, synaptic vesicle-associated proteins synapsin I and II leads to severe reductions in the number of synaptic vesicles in the CNS. We here define the postnatal developmental period during which the synapsin I and/or II proteins modulate synaptic vesicle number and function in excitatory glutamatergic synapses in mouse brain. In wild-type mice, brain levels of both synapsin I and synapsin IIb showed developmental increases during synaptogenesis from postnatal days 5-20, while synapsin IIa showed a protracted increase during postnatal days 20-30. The vesicular glutamate transporters (VGLUT) 1 and VGLUT2 showed synapsin-independent development during postnatal days 5-10, following which significant reductions were seen when synapsin-deficient brains were compared with wild-type brains following postnatal day 20. A similar, synapsin-dependent developmental profile of vesicular glutamate uptake occurred during the same age periods. Physiological analysis of the development of excitatory glutamatergic synapses, performed in the CA1 stratum radiatum of the hippocampus from the two genotypes, showed that both the synapsin-dependent part of the frequency facilitation and the synapsin-dependent delayed response enhancement were restricted to the period after postnatal day 10. Our data demonstrate that while both synaptic vesicle number and presynaptic short-term plasticity are essentially independent of synapsin I and II prior to postnatal day 10, maturation and function of excitatory synapses appear to be strongly dependent on synapsin I and II from postnatal day 20.
Bogen
I L
IL
Department of Biochemistry, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, P.O. Box 1112 Blindern, NO-0317 Oslo, Norway.
Jensen
V
V
Hvalby
O
O
Walaas
S I
SI
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
C493465:Slc17a7 protein, mouse; D016704:Synapsins; D050598:Vesicular Glutamate Transport Protein 1; D018698:Glutamic Acid