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Functional analysis of neurotransmission at β2‐laminin deficient terminals
Author(s) -
Knight David,
Tolley Lynn K.,
Kim David K.,
Lavidis Nick A.,
Noakes Peter G.
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.030924
Subject(s) - laminin , neurotransmission , synaptic vesicle , extracellular , biology , neurotransmitter , mutant , endocrinology , medicine , microbiology and biotechnology , biophysics , neuroscience , chemistry , vesicle , receptor , biochemistry , gene , central nervous system , extracellular matrix , membrane
β2‐Laminin is important for the formation of neuromuscular junctions in vertebrates. Previously, we have inactivated the gene that encodes for β2‐laminin in mice and observed predominantly prejunctional structural defects. In this study, we have used both intra‐ and extracellular recording methods to investigate evoked neurotransmission in β2‐laminin‐deficient mice, from postnatal day 8 (P8) through to day 18 (P18). Our results confirmed that there was a decrease in the frequency of spontaneous release, but no change in the postjunctional response to such release. Analysis of evoked neurotransmission showed an increase in the frequency of stimuli that failed to elicit an evoked postjunctional response in the mutants compared to litter mate controls, resulting in a 50 % reduction in mean quantal content at mutant terminals. Compared to littermate controls, β2‐laminin‐deficient terminals showed greater synaptic depression when subjected to high frequency stimulation. Furthermore, the paired pulse ratio of the first two stimuli was significantly lower in β2‐laminin mutant terminals. Statistical analysis of the binomial parameters of release showed that the decrease in quantal content was due to a decrease in the number of release sites without any significant change in the average probability of release. This suggestion was supported by the observation of fewer synaptic vesicle protein 2 (SV2)‐positive varicosities in β2‐laminin‐deficient terminals and by ultrastructural observations showing smaller terminal profiles and increased Schwann cell invasion in β2‐laminin mutants; the differences between β2‐laminin mutants and wild‐type mice were the same at both P8 and P18. From these results we conclude that β2‐laminin plays a role in the early structural development of the neuromuscular junction. We also suggest that transmitter release activity may act as a deterrent to Schwann cell invasion in the absence of β2‐laminin.