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Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats.
Behav Brain Res 2016; 301:43-54BB

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+Show Affiliations

Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.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.CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81531-980, PR, Brazil.Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal; Departamento de Farmacologia e Terapêuticas Experimentais/IBILI, Universidade de Coimbra, Portugal.Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis 88049-900, SC, Brazil.Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81531-980, PR, Brazil.CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3005-504 Coimbra, Portugal.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26707254

Citation

Matheus, Filipe C., et al. "Decreased Synaptic Plasticity in the Medial Prefrontal Cortex Underlies Short-term Memory Deficits in 6-OHDA-lesioned Rats." Behavioural Brain Research, vol. 301, 2016, pp. 43-54.
Matheus FC, Rial D, Real JI, et al. Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats. Behav Brain Res. 2016;301:43-54.
Matheus, F. C., Rial, D., Real, J. I., Lemos, C., Ben, J., Guaita, G. O., ... Prediger, R. D. (2016). Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats. Behavioural Brain Research, 301, pp. 43-54. doi:10.1016/j.bbr.2015.12.011.
Matheus FC, et al. Decreased Synaptic Plasticity in the Medial Prefrontal Cortex Underlies Short-term Memory Deficits in 6-OHDA-lesioned Rats. Behav Brain Res. 2016 Mar 15;301:43-54. PubMed PMID: 26707254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats. AU - Matheus,Filipe C, AU - Rial,Daniel, AU - Real,Joana I, AU - Lemos,Cristina, AU - Ben,Juliana, AU - Guaita,Gisele O, AU - Pita,Inês R, AU - Sequeira,Ana C, AU - Pereira,Frederico C, AU - Walz,Roger, AU - Takahashi,Reinaldo N, AU - Bertoglio,Leandro J, AU - Da Cunha,Cláudio, AU - Cunha,Rodrigo A, AU - Prediger,Rui D, Y1 - 2015/12/18/ PY - 2015/09/04/received PY - 2015/12/05/revised PY - 2015/12/11/accepted PY - 2015/12/29/entrez PY - 2015/12/29/pubmed PY - 2016/10/21/medline KW - 6-OHDA KW - Dorsolateral striatum KW - Medial prefrontal cortex KW - Non-motor symptoms KW - Parkinson’s disease KW - Short-term memory SP - 43 EP - 54 JF - Behavioural brain research JO - Behav. Brain Res. VL - 301 N2 - 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. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/26707254/Decreased_synaptic_plasticity_in_the_medial_prefrontal_cortex_underlies_short_term_memory_deficits_in_6_OHDA_lesioned_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(15)30324-7 DB - PRIME DP - Unbound Medicine ER -