Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1
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Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1. / Law, Janice W S; Lee, Alan Y W; Sun, Mu; Nikonenko, Alexander G; Chung, Sookja K; Dityatev, Alexander; Schachner, Melitta; Morellini, Fabio.
In: J NEUROSCI, Vol. 23, No. 32, 12.11.2003, p. 10419-32.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Decreased anxiety, altered place learning, and increased CA1 basal excitatory synaptic transmission in mice with conditional ablation of the neural cell adhesion molecule L1
AU - Law, Janice W S
AU - Lee, Alan Y W
AU - Sun, Mu
AU - Nikonenko, Alexander G
AU - Chung, Sookja K
AU - Dityatev, Alexander
AU - Schachner, Melitta
AU - Morellini, Fabio
PY - 2003/11/12
Y1 - 2003/11/12
N2 - 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.
AB - 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.
KW - Animals
KW - Anxiety
KW - Behavior, Animal
KW - Chimera
KW - Electrophysiology
KW - Gene Targeting
KW - Hippocampus
KW - Immunohistochemistry
KW - Integrases
KW - Learning
KW - Long-Term Potentiation
KW - Male
KW - Maze Learning
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Mutant Strains
KW - Mice, Transgenic
KW - Motor Activity
KW - Neural Cell Adhesion Molecule L1
KW - Neuronal Plasticity
KW - Prosencephalon
KW - Spatial Behavior
KW - Synaptic Transmission
KW - Viral Proteins
M3 - SCORING: Journal article
C2 - 14614101
VL - 23
SP - 10419
EP - 10432
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 32
ER -