Dg

References

NCAM-/-

*

n.d.

*

*

(36,52,56)

NCAMff+

*

*

=

n.d.

(50)

Endo-N

*

*

=

n.d.

(36,20)

PST-/-

*

*

=

=

(54,56)

STX-/-

=

n.d.

=

=

(55,56)

Abbreviations: DG, dentate gyrus; NCAMff+, conditional NCAM-deficient mice; impaired; =, normal; n.d., not determined

Abbreviations: DG, dentate gyrus; NCAMff+, conditional NCAM-deficient mice; impaired; =, normal; n.d., not determined could be spectrin, which has been reported to bind to these two molecules and is highly expressed in postsynaptic densities27'48'59. Because PSA may directly potentiate opening of AMPA-type glutamate receptors22, another interesting possibility would be that PSA influences activity of NMDA receptors via a direct interaction with the extracellular domain of receptors.

The results showing the role of NCAM in hippocampal plasticity are nicely complemented by studies of hippocampus-dependent forms of learning and memory. Perturbation of NCAM function with NCAM antibodies caused amnesia in a passive avoidance task60 and defects in spatial learning in rats61. Constitutively and conditionally NCAM-deficient mice show a deficit in spatial learning in the Morris water maze paradigm50,51. Mutant mice either lacking NCAM, or transgenically designed to overproduce soluble extracellular fragments of NCAM, or deficient in the polysialyltransferase ST8SiaII, all show impaired contextual and cued fear memories556263. Consistent with this, an enzymatic removal of PSA and injection of a synthetic dendropeptide C3d that binds to the first Ig domain of NCAM show impaired contextual memory in a fear-conditioning paradigm53,64. In contrast, the NCAM-derived peptide, FGL, corresponding to the binding site of NCAM to FGF receptors, improves long-lasting retrieval of fear memory43.

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