title: Physiological and morphological plasticity induced by chronic treatment with NT-3 or NT-4/5 in hippocampal slice cultures.
abstract: Expression of neurotrophins (NTs) and their receptors is elevated in the adult CNS under several neuropathological conditions. We have investigated the anatomical and electrophysiological consequences of chronic NT-3 or NT-4/5 treatment on established organotypic hippocampal slice cultures maintained in vitro for > 14 days. Both NT-3 and NT-4/5 increased spontaneous, action potential-dependent excitatory synaptic activity (sEPSCs), but only NT-3 increased inhibitory synaptic activity (sIPSCs) in CA3 pyramidal cells. Both NTs strongly promoted spontaneous synaptic bursting activity. Spontaneous bursts of EPSCs were observed after either NT treatment but only NT-3-treated cultures exhibited an increase in spontaneous bursts of IPSCs. In addition, sIPSC bursts were eliminated by blocking glutamatergic excitation. The frequency of miniature inhibitory postsynaptic currents, but not miniature excitatory postsynaptic currents, was also increased by both NT-3 and NT-4/5. Furthermore, NT-3 and NT-4/5 induced an up-regulation of the growth-associated protein GAP-43, suggesting that neurotrophins may be able to induce axonal reorganization in established neuronal networks. CA1 pyramidal cells exhibited slight alterations in dendritic branching after NT-4/5, but not NT-3 treatment. We conclude that chronic treatment with NT-3 or NT-4/5 can affect an established hippocampal network by elevating spontaneous inhibitory and excitatory synaptic activity and inducing coordinated pre- and postsynaptic structural changes.
authors.affiliation: Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Schwyzer
authors.forename: José María
authors.initials: JM
authors.lastname: Mateos
authors.forename: Mathias
authors.initials: M
authors.lastname: Abegg
authors.forename: Lotty
authors.initials: L
authors.lastname: Rietschin
authors.forename: Lucette
authors.initials: L
authors.lastname: Heeb
authors.forename: Scott M
authors.initials: SM
authors.lastname: Thompson
authors.forename: Andreas
authors.initials: A
authors.lastname: Lüthi
authors.forename: Beat H
authors.initials: BH
authors.lastname: Gähwiler
authors.forename: R Anne
authors.initials: RA
authors.lastname: McKinney
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects; D046508:Culture Techniques; D003712:Dendrites / Q000187:drug effects; D019922:GAP-43 Protein / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D019922:GAP-43 Protein; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; C071951:neurotrophin 5; C073922:neurotrophin 4