Loss of cadherin-11 adhesion receptor enhances plastic changes in hippocampal synapses and modifies behavioral responses.
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.
Manabe
T
T
Department of Neurophysiology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033, USA.
Togashi
H
H
Uchida
N
N
Suzuki
S C
SC
Hayakawa
Y
Y
Yamamoto
M
M
Yoda
H
H
Miyakawa
T
T
Takeichi
M
M
Chisaka
O
O
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000166:cytology; D001923:Brain Chemistry / Q000235:genetics; D015820:Cadherins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D013216:Reflex, Startle / Q000502:physiology; D013569:Synapses / Q000737:chemistry / Q000378:metabolism*
D015820:Cadherins; D012333:RNA, Messenger; C086960:osteoblast cadherin