The polysialic acid modification of the neural cell adhesion molecule is involved in spatial learning and hippocampal long-term potentiation.
The alpha-2,8-linked polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) modulates morphogenetic cell interactions. PSA is strongly expressed during neural development and generally down-regulated in the adult. However, it remains prominent in some areas of the brain, e.g., the hippocampus. We assayed the functional role(s) of PSA in synaptic plasticity in the hippocampus in two experimental paradigms by removing PSA with endo-neuraminidase NE (endo-N) an enzyme which specifically cleaves alpha-2,8-linked polysialic acid. (1) The acquisition and retention of spatial memory of rats in the Morris water maze, critically dependent on the hippocampus, was significantly impaired after a localized injection of endo-N into the hippocampus, whereas visual and motor capacities were unaffected. (2) Tetanic stimulation of the Schaffer collaterals in endo-N-treated hippocampal slices in vitro failed to elicit LTP and yielded only a short post-tetanic potentiation, but the response returned to control levels within 2 minutes, whereas basal synaptic activity and short-term potentiation were not affected. Our findings suggest that the carbohydrate epitope PSA plays an important role in synaptic plasticity.
Becker
C G
CG
Dept. Neurobiology, Swiss Federal Institute of Technology Zürich, Hönggerberg, Zürich, Switzerland.
Artola
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A
Gerardy-Schahn
R
R
Becker
T
T
Welzl
H
H
Schachner
M
M
D000704:Analysis of Variance; D000818:Animals; D004924:Escape Reaction; D006026:Glycoside Hydrolases / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time; D012794:Sialic Acids / Q000502:physiology*
D039842:Neural Cell Adhesion Molecule L1; D019006:Neural Cell Adhesion Molecules; D012794:Sialic Acids; C021319:polysialic acid; C103469:polysialyl neural cell adhesion molecule; D006026:Glycoside Hydrolases; C090534:endo-alpha-sialidase