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Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.

Publication ,  Journal Article
Li, L; Chin, LS; Shupliakov, O; Brodin, L; Sihra, TS; Hvalby, O; Jensen, V; Zheng, D; McNamara, JO; Greengard, P
Published in: Proc Natl Acad Sci U S A
September 26, 1995

Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exocytosis. To further understand the role of synapsin I in the function of adult nerve terminals, we studied synapsin I-deficient mice generated by homologous recombination. The organization of synaptic vesicles at presynaptic terminals of synapsin I-deficient mice was markedly altered: densely packed vesicles were only present in a narrow rim at active zones, whereas the majority of vesicles were dispersed throughout the terminal area. This was in contrast to the organized vesicle clusters present in terminals of wild-type animals. Release of glutamate from nerve endings, induced by K+,4-aminopyridine, or a Ca2+ ionophore, was markedly decreased in synapsin I mutant mice. The recovery of synaptic transmission after depletion of neurotransmitter by high-frequency stimulation was greatly delayed. Finally, synapsin I-deficient mice exhibited a strikingly increased response to electrical stimulation, as measured by electrographic and behavioral seizures. These results provide strong support for the hypothesis that synapsin I plays a key role in the regulation of nerve terminal function in mature synapses.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 26, 1995

Volume

92

Issue

20

Start / End Page

9235 / 9239

Location

United States

Related Subject Headings

  • Synaptosomes
  • Synaptic Vesicles
  • Synaptic Transmission
  • Synapsins
  • Synapses
  • Seizures
  • Reference Values
  • Receptors, Glutamate
  • Microscopy, Electron
  • Mice, Neurologic Mutants
 

Citation

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Li, L., Chin, L. S., Shupliakov, O., Brodin, L., Sihra, T. S., Hvalby, O., … Greengard, P. (1995). Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci U S A, 92(20), 9235–9239. https://doi.org/10.1073/pnas.92.20.9235
Li, L., L. S. Chin, O. Shupliakov, L. Brodin, T. S. Sihra, O. Hvalby, V. Jensen, D. Zheng, J. O. McNamara, and P. Greengard. “Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.Proc Natl Acad Sci U S A 92, no. 20 (September 26, 1995): 9235–39. https://doi.org/10.1073/pnas.92.20.9235.
Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS, Hvalby O, et al. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9235–9.
Li, L., et al. “Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.Proc Natl Acad Sci U S A, vol. 92, no. 20, Sept. 1995, pp. 9235–39. Pubmed, doi:10.1073/pnas.92.20.9235.
Li L, Chin LS, Shupliakov O, Brodin L, Sihra TS, Hvalby O, Jensen V, Zheng D, McNamara JO, Greengard P. Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice. Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9235–9239.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

September 26, 1995

Volume

92

Issue

20

Start / End Page

9235 / 9239

Location

United States

Related Subject Headings

  • Synaptosomes
  • Synaptic Vesicles
  • Synaptic Transmission
  • Synapsins
  • Synapses
  • Seizures
  • Reference Values
  • Receptors, Glutamate
  • Microscopy, Electron
  • Mice, Neurologic Mutants