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

Abstract

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.

Ontogeny of postsynaptic density proteins at glutamatergic synapses

“…In fact, NCAM180 associates with NR2A-containing NMDA receptors in the central region of the postsynaptic membrane in hippocampus; this distribution changes following induction of long-term potentiation in vivo in adult rodents (Fux et al, 2003) where NCAMs help mediate synaptic plasticity (Bukalo et al, 2004). Similar to NCAMs, members of the L1 family are important both in synaptogenesis (Faivre-Sarrailh et al, 1999;Suh et al, 2004) and for synaptic plasticity in adult brain (Law et al, 2003).…”

The adhesion molecule L1 regulates transendothelial migration and trafficking of dendritic cells

“…The tyrosine kinase receptor Tie2 is expressed in early precursors of hematopoietic and ECs ( 7 ). Hence, transgenic mice expressing Cre recombinase under the control of the Tie2 gene promoter ( 8 ) were intercrossed with L1 f loxed mice carrying two f loxed alleles of the L1cam gene ( 9 ). The genotype of the mice was determined by PCR on genomic DNA ( Fig.…”

Neural Cell Adhesion Molecule L1-Transfected Embryonic Stem Cells Promote Functional Recovery after Excitotoxic Lesion of the Mouse Striatum

“…Among the recognition molecules that mediate these functions is L1, a homophilically and heterophilically binding member of the Ig superfamily that is expressed by neurons but not by astrocytes and oligodendrocytes in the CNS and by neurons and Schwann cells in the peripheral nervous system (Lindner et al, 1983;Rathjen and Schachner, 1984;Moos et al, 1988;Appel et al, 1993;Kamiguchi and Yoshihara, 2001). L1 promotes neuronal survival, neurite outgrowth (Lemmon et al, 1989;Appel et al, 1993;Chen et al, 1999;Kleene et al, 2001;Dong et al, 2003), and synaptic plasticity, as shown by modification of synaptic efficacy both in vitro and in vivo as well as in learning and memory as seen in L1-deficient mice and humans (Luthi et al, 1996;Fransen et al, 1998a,b;Tiunova et al, 1998;Wolfer et al, 1998;Demyanenko et al, 1999;Pradel et al, 2000;Law et al, 2003;Saghatelyan et al, 2004;Venero et al, 2004). Furthermore, L1 is involved in myelination in the central and peripheral nervous systems (Seilheimer et al, 1989;Wood et al, 1990;Haney et al, 1999;Barbin et al, 2004).…”