title: The neural cell adhesion molecule-derived peptide FGL facilitates long-term plasticity in the dentate gyrus in vivo.
abstract: The neural cell adhesion molecule (NCAM) is known to play a role in developmental and structural processes but also in synaptic plasticity and memory of the adult animal. Recently, FGL, a NCAM mimetic peptide that binds to the Fibroblast Growth Factor Receptor 1 (FGFR-1), has been shown to have a beneficial impact on normal memory functioning, as well as to rescue some pathological cognitive impairments. Whether its facilitating impact may be mediated through promoting neuronal plasticity is not known. The present study was therefore designed to test whether FGL modulates the induction and maintenance of synaptic plasticity in the dentate gyrus (DG) in vivo. For this, we first assessed the effect of the FGL peptide on synaptic functions at perforant path-dentate gyrus synapses in the anesthetized rat. FGL, or its control inactive peptide, was injected locally 60 min before applying high-frequency stimulation (HFS) to the medial perforant path. The results suggest that although FGL did not alter basal synaptic transmission, it facilitated both the induction and maintenance of LTP. Interestingly, FGL also modified the heterosynaptic plasticity observed at the neighboring lateral perforant path synapses. The second series of experiments, using FGL intracerebroventricular infusion in the awake animal, confirmed its facilitating effect on LTP for up to 24 h. Our data also suggest that FGL could alter neurogenesis associated with LTP. In sum, these results show for the first time that enhancing NCAM functions by mimicking its heterophilic interaction with FGFR facilitates hippocampal synaptic plasticity in the awake, freely moving animal.
authors.affiliation: Centre de Neurosciences Paris-Sud, Université Paris-Sud XI, CNRS-UMR8195, 91405, Orsay, France.
authors.forename: Glenn
authors.initials: G
authors.lastname: Dallérac
authors.forename: Meike
authors.initials: M
authors.lastname: Zerwas
authors.forename: Tatiana
authors.initials: T
authors.lastname: Novikova
authors.forename: Delphine
authors.initials: D
authors.lastname: Callu
authors.forename: Pascale
authors.initials: P
authors.lastname: Leblanc-Veyrac
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bock
authors.forename: Vladimir
authors.initials: V
authors.lastname: Berezin
authors.forename: Claire
authors.initials: C
authors.lastname: Rampon
authors.forename: Valérie
authors.initials: V
authors.lastname: Doyère
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism* / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: C488618:NCAM protein (681-695), human; D019006:Neural Cell Adhesion Molecules