Intrahippocampal administration of an antibody against the HNK-1 carbohydrate impairs memory consolidation in an inhibitory learning task in mice.
Many cell adhesion molecules express the HNK-1 carbohydrate involved in formation and functioning of synapses. To assess its role in learning, we injected the monoclonal HNK-1 antibody or nonimmune IgG into the hippocampus of C57BL/6J mice 1 h after training in a step-down avoidance task. In animals treated with the HNK-1 antibody, latencies of step down in a recall session 48 h after injection did not change compared to training values and were significantly shorter versus IgG-treated controls, which acquired the task normally. Similar differences between the two treatments were also observed after a stronger training protocol in a step-down avoidance paradigm. The HNK-1 antibody was effective only when injected 1 h, but not 48 h after training, thus affecting memory consolidation but not memory recall itself. The HNK-1 antibody impaired memory also in tenascin-R knock-out mice, indicating that extracellular matrix molecule tenascin-R, one of the carriers of the HNK-1epitope in the hippocampus, does not mediate the function of the HNK-1 carbohydrate in this task. Our observations show that the HNK-1 carbohydrate is critically involved in memory consolidation in hippocampus-dependent learning in mammals.
Strekalova
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T
Zentrum für Molekulare Neurobiologie, Universität Hamburg, Martinistrasse 52, Hamburg, D-20246, Germany.
Wotjak
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CT
Schachner
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M
D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D018959:CD57 Antigens / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*
D000906:Antibodies; D018959:CD57 Antigens; D015816:Cell Adhesion Molecules, Neuronal