Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1.
L1, a neural cell adhesion molecule of the immunoglobulin superfamily, is involved in neuronal migration and differentiation and axon outgrowth and guidance. Mutations in the human and mouse L1 gene result in similarly severe neurological abnormalities. To dissociate the functional roles of L1 in the adult brain from developmental abnormalities, we have generated a mutant in which the L1 gene is inactivated by cre-recombinase under the control of the calcium/calmodulin-dependent kinase II promoter. This mutant (L1fy+) did not show the overt morphological and behavioral abnormalities observed previously in constitutive L1-deficient (L1-/-) mice; however, there was an increase in basal excitatory synaptic transmission that was not apparent in L1-/- mice. Similar to L1-/- mice, no defects in short- and long-term potentiation in the CA1 region of the hippocampus were observed. Interestingly, L1fy+ mice showed decreased anxiety in the open field and elevated plus-maze, contrary to L1-/- mice, and altered place learning in the water maze, similar to L1-/- mice. Thus, mice conditionally deficient in L1 expression in the adult brain share some abnormalities, but also display different ones, as compared with L1-/- mice, highlighting the role of L1 in the regulation of synaptic transmission and behavior in adulthood.
Law
Janice W S
JW
Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany.
Lee
Alan Y W
AY
Sun
Mu
M
Nikonenko
Alexander G
AG
Chung
Sookja K
SK
Dityatev
Alexander
A
Schachner
Melitta
M
Morellini
Fabio
F
D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001522:Behavior, Animal / Q000502:physiology; D002678:Chimera; D004594:Electrophysiology; D018390:Gene Targeting / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D007150:Immunohistochemistry; D019426:Integrases / Q000096:biosynthesis / Q000235:genetics; D007858:Learning / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D039842:Neural Cell Adhesion Molecule L1 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism; D013037:Spatial Behavior / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics
D039842:Neural Cell Adhesion Molecule L1; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases