Reduction of hippocampal long-term potentiation in transgenic mice ectopically expressing the neural cell adhesion molecule L1 in astrocytes.
The influence of the neural cell adhesion molecule L1 on hippocampal long-term potentiation (LTP) was investigated using transgenic mice ectopically expressing L1 in astrocytes (GFAP-L1). L1 is a member of the immunoglobulin superfamily of homophilic adhesion molecules predominantly expressed in neurones. Previously, it has been demonstrated that local application of L1 antibodies and recombinant L1 fragments impair the expression of LTP. Here, we show that LTP induced by theta-burst stimulation or by pairing presynaptic stimulation with postsynaptic depolarisation was strongly reduced in GFAP-L1 mice, whereas basal synaptic transmission, post-tetanic potentiation, and paired-pulse facilitation were not modified. These results further support the idea that L1 is involved in synaptic plasticity and suggest that adhesion molecule-dependent changes in synaptic morphology contribute to the expression of LTP.
Pharma Division, F. Hoffmann-La roche Ltd, Basel, Switzerland.
A
A
Lüthi
H
H
Mohajeri
M
M
Schachner
J P
JP
Laurent
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D039841:Leukocyte L1 Antigen Complex; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics*; D017966:Pyramidal Cells / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000502:physiology; D013826:Theta Rhythm
D039841:Leukocyte L1 Antigen Complex; D019006:Neural Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate