Reduced GABAergic transmission and number of hippocampal perisomatic inhibitory synapses in juvenile mice deficient in the neural cell adhesion molecule L1.
Cell adhesion molecules have been implicated in neural development and hippocampal synaptic plasticity. Here, we investigated the role of the neural cell adhesion molecule L1 in regulation of basal synaptic transmission and plasticity in the CA1 area of the hippocampus of juvenile mice. We show that theta-burst stimulation (TBS) and pairing of low-frequency presynaptic stimulation with depolarization of postsynaptic CA1 pyramidal cells induced similar levels of LTP in L1-deficient and wild-type mice. The basal excitatory synaptic transmission and density of asymmetric excitatory synapses in the stratum radiatum were also normal in L1-deficient mice. Since L1 is expressed not only by principal cells but also by inhibitory interneurons, we recorded inhibitory postsynaptic currents (IPSCs) evoked in CA1 pyramidal cells by minimal stimulation of perisomatic interneurons. L1-deficient mice showed a reduction in the mean amplitude of putative unitary IPSCs, higher values of the coefficient of amplitude variation, higher number of failures in transmitter release, and a reduction in frequency but not amplitude of miniature IPSCs. The use-dependent modulation of inhibitory transmission by paired-pulse or short tetanic stimulation was, however, normal in L1-deficient mice. The physiological abnormalities correlated with a strong reduction in the density of inhibitory active zones, indicating that L1 is involved in establishing inhibitory perisomatic synapses in the hippocampus.
Saghatelyan
Armen K
AK
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany.
Nikonenko
Alexander G
AG
Sun
Mu
M
Rolf
Bettina
B
Putthoff
Peggy
P
Kutsche
Michael
M
Bartsch
Udo
U
Dityatev
Alexander
A
Schachner
Melitta
M
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D004558:Electric Stimulation; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency* / Q000235:genetics; D009433:Neural Inhibition / Q000235:genetics*; D017966:Pyramidal Cells / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*; D013826:Theta Rhythm; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D039842:Neural Cell Adhesion Molecule L1; D005680:gamma-Aminobutyric Acid