title: Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory.
abstract: Extracellular signal-regulated kinases (ERK1 and 2) are synaptic signaling components necessary for several forms of learning. In mice lacking ERK1, we observe a dramatic enhancement of striatum-dependent long-term memory, which correlates with a facilitation of long-term potentiation in the nucleus accumbens. At the cellular level, we find that ablation of ERK1 results in a stimulus-dependent increase of ERK2 signaling, likely due to its enhanced interaction with the upstream kinase MEK. Consistently, such activity change is responsible for the hypersensitivity of ERK1 mutant mice to the rewarding properties of morphine. Our results reveal an unexpected complexity of ERK-dependent signaling in the brain and a critical regulatory role for ERK1 in the long-term adaptive changes underlying striatum-dependent behavioral plasticity and drug addiction.
authors.affiliation: San Raffaele Research Institute and University, via Olgettina 58, 20132 Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzucchelli
authors.forename: Chiara
authors.initials: C
authors.lastname: Vantaggiato
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ciamei
authors.forename: Stefania
authors.initials: S
authors.lastname: Fasano
authors.forename: Pavel
authors.initials: P
authors.lastname: Pakhotin
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krezel
authors.forename: Hans
authors.initials: H
authors.lastname: Welzl
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.forename: Gilles
authors.initials: G
authors.lastname: Pagès
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
authors.forename: Anne
authors.initials: A
authors.lastname: Marowsky
authors.forename: Annamaria
authors.initials: A
authors.lastname: Porrazzo
authors.forename: Paul C
authors.initials: PC
authors.lastname: Orban
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Markus U
authors.initials: MU
authors.lastname: Ehrengruber
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cestari
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Lipp
authors.forename: Paul F
authors.initials: PF
authors.lastname: Chapman
authors.forename: Jacques
authors.initials: J
authors.lastname: Pouysségur
authors.forename: Riccardo
authors.initials: R
authors.lastname: Brambilla
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000201:enzymology; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003072:Cognition Disorders / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D003342:Corpus Striatum / Q000002:abnormalities / Q000166:cytology / Q000201:enzymology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D017774:Long-Term Potentiation / Q000235:genetics*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency* / Q000235:genetics; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000002:abnormalities / Q000166:cytology / Q000201:enzymology; D009421:Nervous System Malformations / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009714:Nucleus Accumbens / Q000002:abnormalities / Q000166:cytology / Q000201:enzymology*; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D009020:Morphine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases