TY - JOUR
T1 - Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses
AU - Manabe, Toshiya
AU - Togashi, Hideru
AU - Uchida, Naoshige
AU - Suzuki, Sachihiro C.
AU - Hayakawa, Yoshizumi
AU - Yamamoto, Masaru
AU - Yoda, Hiroki
AU - Miyakawa, Tsuyoshi
AU - Takeichi, Masatoshi
AU - Chisaka, Osamu
N1 - Funding Information:
We thank T. Takahashi for comments on the manuscript, H. Niki, N. Hironaka, M. Yokoi, M. Masugi, and S. Nakanishi for advice and comments on behavior tests, S. Takada for advice on gene targeting, K. Nishimura and Y. Kurotaki for production of chimeric mice, M. J. Wheelock and K. Knudsen for antibodies, N. Tamamaki for anatomical analysis, S. Tsukita for electron microscopy, D. Fushimi for advice on hippocampal cultures, and M. Aiso for preparation of the manuscript. This work was supported by the program Grants-in-Aid for Creative Fundamental Research and for Specially Promoted Research (M.T.), and other grants (T. Manabe and O.C.) from the Ministry of Education, Science, Sports, and Culture of Japan; and by grants from the Uehara Memorial Foundation, the Mitsubishi Foundation, and the Research for the Future Program by the Japan Society for the Promotion of Sciences (T. Manabe).
PY - 2000/6
Y1 - 2000/6
N2 - Cadherins organize symmetrical junctions between the pre- and postsynaptic membranes in central synapses. One of them, cadherin-11 (cad11), is expressed in the limbic system of the brain, most strongly in the hippocampus. Immunohistochemical studies of the hippocampus showed that cad11 proteins were densely distributed in its synaptic neuropil zones; in cultured hippocampal neurons, their distribution often overlapped with that of synaptophysin, and also occasionally with that of GluR1 at spines. To assess the role of cad11 in synaptic formation and/or function, we analyzed brains of cad11-deficient mice. In these mice, long-term potentiation (LTP) in the CA1 region of the hippocampus was, unexpectedly, enhanced; and the level of LTP saturation was increased. In behavioral tests, the mutant mice showed reduced fear-or anxiety-related responses. These results suggest that the cad11-mediated junctions may modulate synaptic efficacy, confining its dynamic changes to a limited range, or these junctions are required for normal development of synaptic organization in the hippocampus.
AB - Cadherins organize symmetrical junctions between the pre- and postsynaptic membranes in central synapses. One of them, cadherin-11 (cad11), is expressed in the limbic system of the brain, most strongly in the hippocampus. Immunohistochemical studies of the hippocampus showed that cad11 proteins were densely distributed in its synaptic neuropil zones; in cultured hippocampal neurons, their distribution often overlapped with that of synaptophysin, and also occasionally with that of GluR1 at spines. To assess the role of cad11 in synaptic formation and/or function, we analyzed brains of cad11-deficient mice. In these mice, long-term potentiation (LTP) in the CA1 region of the hippocampus was, unexpectedly, enhanced; and the level of LTP saturation was increased. In behavioral tests, the mutant mice showed reduced fear-or anxiety-related responses. These results suggest that the cad11-mediated junctions may modulate synaptic efficacy, confining its dynamic changes to a limited range, or these junctions are required for normal development of synaptic organization in the hippocampus.
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U2 - 10.1006/mcne.2000.0849
DO - 10.1006/mcne.2000.0849
M3 - Article
C2 - 10860580
AN - SCOPUS:0033945407
SN - 1044-7431
VL - 15
SP - 534
EP - 546
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 6
ER -