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Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus.
J Neurosci 2004; 24(7):1565-77JN

Abstract

NCAM, a neural cell adhesion molecule of the immunoglobulin superfamily, is involved in neuronal migration and differentiation, axon outgrowth and fasciculation, and synaptic plasticity. To dissociate the functional roles of NCAM in the adult brain from developmental abnormalities, we generated a mutant in which the NCAM gene is inactivated by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter, resulting in reduction of NCAM expression predominantly in the hippocampus. This mutant (NCAMff+) did not show the overt morphological and behavioral abnormalities previously observed in constitutive NCAM-deficient (NCAM-/-) mice. However, similar to the NCAM-/- mouse, a reduction in long-term potentiation (LTP) in the CA1 region of the hippocampus was revealed. Long-term depression was also abolished in NCAMff+ mice. The deficit in LTP could be rescued by elevation of extracellular Ca2+ concentrations from 1.5 or 2.0 to 2.5 mm, suggesting an involvement of NCAM in regulation of Ca2+-dependent signaling during LTP. Contrary to the NCAM-/- mouse, LTP in the CA3 region was normal, consistent with normal mossy fiber lamination in NCAMff+ as opposed to abnormal lamination in NCAM-/- mice. NCAMff+ mutants did not show general deficits in short- and long-term memory in global landmark navigation in the water maze but were delayed in the acquisition of precise spatial orientation, a deficit that could be overcome by training. Thus, mice conditionally deficient in hippocampal NCAM expression in the adult share certain abnormalities characteristic of NCAM-/- mice, highlighting the role of NCAM in the regulation of synaptic plasticity in the CA1 region.

Authors+Show Affiliations

Zentrum fuer Molekulare Neurobiologie, Universitaet Hamburg, D-20246 Hamburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14973228

Citation

Bukalo, Olena, et al. "Conditional Ablation of the Neural Cell Adhesion Molecule Reduces Precision of Spatial Learning, Long-term Potentiation, and Depression in the CA1 Subfield of Mouse Hippocampus." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 24, no. 7, 2004, pp. 1565-77.
Bukalo O, Fentrop N, Lee AY, et al. Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. J Neurosci. 2004;24(7):1565-77.
Bukalo, O., Fentrop, N., Lee, A. Y., Salmen, B., Law, J. W., Wotjak, C. T., ... Schachner, M. (2004). Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 24(7), pp. 1565-77.
Bukalo O, et al. Conditional Ablation of the Neural Cell Adhesion Molecule Reduces Precision of Spatial Learning, Long-term Potentiation, and Depression in the CA1 Subfield of Mouse Hippocampus. J Neurosci. 2004 Feb 18;24(7):1565-77. PubMed PMID: 14973228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Conditional ablation of the neural cell adhesion molecule reduces precision of spatial learning, long-term potentiation, and depression in the CA1 subfield of mouse hippocampus. AU - Bukalo,Olena, AU - Fentrop,Nikolas, AU - Lee,Alan Y W, AU - Salmen,Benedikt, AU - Law,Janice W S, AU - Wotjak,Carsten T, AU - Schweizer,Michaela, AU - Dityatev,Alexander, AU - Schachner,Melitta, PY - 2004/2/20/pubmed PY - 2004/5/5/medline PY - 2004/2/20/entrez SP - 1565 EP - 77 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 24 IS - 7 N2 - NCAM, a neural cell adhesion molecule of the immunoglobulin superfamily, is involved in neuronal migration and differentiation, axon outgrowth and fasciculation, and synaptic plasticity. To dissociate the functional roles of NCAM in the adult brain from developmental abnormalities, we generated a mutant in which the NCAM gene is inactivated by cre-recombinase under the control of the calcium-calmodulin-dependent kinase II promoter, resulting in reduction of NCAM expression predominantly in the hippocampus. This mutant (NCAMff+) did not show the overt morphological and behavioral abnormalities previously observed in constitutive NCAM-deficient (NCAM-/-) mice. However, similar to the NCAM-/- mouse, a reduction in long-term potentiation (LTP) in the CA1 region of the hippocampus was revealed. Long-term depression was also abolished in NCAMff+ mice. The deficit in LTP could be rescued by elevation of extracellular Ca2+ concentrations from 1.5 or 2.0 to 2.5 mm, suggesting an involvement of NCAM in regulation of Ca2+-dependent signaling during LTP. Contrary to the NCAM-/- mouse, LTP in the CA3 region was normal, consistent with normal mossy fiber lamination in NCAMff+ as opposed to abnormal lamination in NCAM-/- mice. NCAMff+ mutants did not show general deficits in short- and long-term memory in global landmark navigation in the water maze but were delayed in the acquisition of precise spatial orientation, a deficit that could be overcome by training. Thus, mice conditionally deficient in hippocampal NCAM expression in the adult share certain abnormalities characteristic of NCAM-/- mice, highlighting the role of NCAM in the regulation of synaptic plasticity in the CA1 region. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/14973228/Conditional_ablation_of_the_neural_cell_adhesion_molecule_reduces_precision_of_spatial_learning_long_term_potentiation_and_depression_in_the_CA1_subfield_of_mouse_hippocampus_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=14973228 DB - PRIME DP - Unbound Medicine ER -