Decreased Anxiety, Altered Place Learning, and Increased CA1 Basal Excitatory Synaptic Transmission in Mice with Conditional Ablation of the Neural Cell Adhesion Molecule L1

• DOI: 10.1523/jneurosci.23-32-10419.2003
• Publication Date: 2018-04-13T22:30:51Z
• Authors: Janice W. S. Law; Alan Y. W. Lee; Mu Sun; Alexander G. Niko...; Sookja K. Chung; Alexander Dityatev; Melitta Schachner; Fabio Morellini
• Keywords: Learning - physiology; Male; Long-Term Potentiation; Viral Proteins - biosynthesis - genetics; Anxiety; Inbred C57BL; Hippocampus; Transgenic; Motor Activity - genetics; Mice; Cell adhesion molecule; 0303 health sciences; Maze Learning - physiology; Neuronal Plasticity; Behavior, Animal; Anxiety - genetics; Hippocampus - cytology - physiology; L1; Immunohistochemistry; Behavior, Animal - physiology; Mutant Strains; Electrophysiology; Spatial Behavior - physiology; Synaptic Transmission - genetics; Gene Targeting; 572; Place learning; Gene Targeting - methods; 610; Mice, Transgenic; Neural Cell Adhesion Molecule L1; Neural Cell Adhesion Molecule L1 - deficiency - genetics - metabolism; Motor Activity; Synaptic plasticity; Integrases - biosynthesis - genetics; Prosencephalon - cytology - metabolism; Long-Term Potentiation - genetics; 03 medical and health sciences; 616; Animals; Learning; Maze Learning; Animal - physiology; Behavior; Integrases; Chimera; Neuronal Plasticity - physiology; Mice, Mutant Strains; Mice, Inbred C57BL

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 inL1-/- mice. Similar toL1-/- 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 toL1-/- mice, and altered place learning in the water maze, similar toL1-/- mice. Thus, mice conditionally deficient in L1 expression in the adult brain share some abnormalities, but also display different ones, as compared withL1-/- mice, highlighting the role of L1 in the regulation of synaptic transmission and behavior in adulthood.