title: Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a gene-environment rat model of depression.
abstract: An animal model of depression combining genetic vulnerability and early-life stress (ELS) was prepared by submitting the Flinders Sensitive Line (FSL) rats to a standard paradigm of maternal separation. We analysed hippocampal synaptic transmission and plasticity in vivo and ionotropic receptors for glutamate in FSL rats, in their controls Flinders Resistant Line (FRL) rats, and in both lines subjected to ELS. A strong inhibition of long-term potentiation (LTP) and lower synaptic expression of NR1 subunit of the NMDA receptor were found in FSL rats. Remarkably, ELS induced a remodelling of synaptic plasticity only in FSL rats, reducing inhibition of LTP; this was accompanied by marked increase of synaptic NR1 subunit and GluR2/3 subunits of AMPA receptors. Chronic treatment with escitalopram inhibited LTP in FRL rats, but this effect was attenuated by prior ELS. The present results suggest that early gene-environment interactions cause lifelong synaptic changes affecting functional and molecular aspects of plasticity, partly reversed by antidepressant treatments.
authors.affiliation: Department of Pharmacology and Therapeutics, Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
authors.forename: Ben
authors.initials: B
authors.lastname: Ryan
authors.forename: Laura
authors.initials: L
authors.lastname: Musazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mallei
authors.forename: Daniela
authors.initials: D
authors.lastname: Tardito
authors.forename: Suzanne H M
authors.initials: SH
authors.lastname: Gruber
authors.forename: Aram
authors.initials: A
authors.lastname: El Khoury
authors.forename: Roger
authors.initials: R
authors.lastname: Anwyl
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Aleksander A
authors.initials: AA
authors.lastname: Mathé
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rowan
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003863:Depression / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D004558:Electric Stimulation; D004594:Electrophysiology; D004777:Environment; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013315:Stress, Psychological / Q000473:pathology* / Q000523:psychology; D013569:Synapses / Q000502:physiology*; D013574:Synaptosomes / Q000502:physiology
chemical_list: D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate