title: Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.
abstract: Parkinson's disease (PD) is characterized by motor dysfunction associated with dopaminergic degeneration in the dorsolateral striatum (DLS). However, motor symptoms in PD are often preceded by short-term memory deficits, which have been argued to involve deregulation of medial prefrontal cortex (mPFC). We now used a 6-hydroxydopamine (6-OHDA) rat PD model to explore if alterations of synaptic plasticity in DLS and mPFC underlie short-term memory impairments in PD prodrome. The bilateral injection of 6-OHDA (20μg/hemisphere) in the DLS caused a marked loss of dopaminergic neurons in the substantia nigra (>80%) and decreased monoamine levels in the striatum and PFC, accompanied by motor deficits evaluated after 21 days in the open field and accelerated rotarod. A lower dose of 6-OHDA (10μg/hemisphere) only induced a partial degeneration (about 60%) of dopaminergic neurons in the substantia nigra with no gross motor impairments, thus mimicking an early premotor stage of PD. Notably, 6-OHDA (10μg)-lesioned rats displayed decreased monoamine levels in the PFC as well as short-term memory deficits evaluated in the novel object discrimination and in the modified Y-maze tasks; this was accompanied by a selective decrease in the amplitude of long-term potentiation in the mPFC, but not in DLS, without changes of synaptic transmission in either brain regions. These results indicate that the short-term memory dysfunction predating the motor alterations in the 6-OHDA model of PD is associated with selective changes of information processing in PFC circuits, typified by persistent changes of synaptic plasticity.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.
authors.forename: Filipe C
authors.initials: FC
authors.lastname: Matheus
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil; CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rial
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Joana I
authors.initials: JI
authors.lastname: Real
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lemos
authors.affiliation: Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Juliana
authors.initials: J
authors.lastname: Ben
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81531-980, PR, Brazil.
authors.forename: Gisele O
authors.initials: GO
authors.lastname: Guaita
authors.affiliation: Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.
authors.forename: Inês R
authors.initials: IR
authors.lastname: Pita
authors.affiliation: Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Sequeira
authors.affiliation: Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.
authors.forename: Frederico C
authors.initials: FC
authors.lastname: Pereira
authors.affiliation: Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.
authors.forename: Leandro J
authors.initials: LJ
authors.lastname: Bertoglio
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81531-980, PR, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Da Cunha
authors.affiliation: CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal.
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Cunha
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil; Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: ruidsp@hotmail.com.
authors.forename: Rui D
authors.initials: RD
authors.lastname: Prediger
mesh_terms: D000818:Animals; D004192:Discrimination, Psychological / Q000502:physiology; D004311:Double-Blind Method; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000473:pathology / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D009043:Motor Activity; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D017208:Rats, Wistar; D045442:Rotarod Performance Test; D065852:Spatial Memory / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D016627:Oxidopamine
keywords: 6-OHDA; Dorsolateral striatum; Medial prefrontal cortex; Non-motor symptoms; Parkinson’s disease; Short-term memory