Decreased synaptic plasticity in the medial prefrontal cortex underlies short-term memory deficits in 6-OHDA-lesioned rats

• Published in: Behavioural brain research 2016-03, Vol.301, p.43-54
• Main Authors: Matheus, Filipe C., Rial, Daniel, Real, Joana I., Lemos, Cristina, Ben, Juliana, Guaita, Gisele O., Pita, Inês R., Sequeira, Ana C., Pereira, Frederico C., Walz, Roger, Takahashi, Reinaldo N., Bertoglio, Leandro J., Cunha, Cláudio Da, Cunha, Rodrigo A., Prediger, Rui D.
• Format: Article
• Language: English
• Subjects: 6-OHDA; Animals; Discrimination (Psychology) - physiology; Dorsolateral striatum; Double-Blind Method; Long-Term Potentiation - physiology; Male; Maze Learning - physiology; Medial prefrontal cortex; Memory Disorders - pathology; Memory Disorders - physiopathology; Memory, Short-Term - physiology; Motor Activity; Non-motor symptoms; Oxidopamine; Parkinsonian Disorders - pathology; Parkinsonian Disorders - physiopathology; Parkinsonian Disorders - psychology; Parkinson’s disease; Prefrontal Cortex - pathology; Prefrontal Cortex - physiopathology; Rats, Wistar; Rotarod Performance Test; Short-term memory; Spatial Memory - physiology; Synaptic Transmission - physiology; Tissue Culture Techniques
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2015.12.011

•Synaptic plasticity impairments in medial prefrontal cortex (mPFC) of 6-OHDA-lesioned rats.•6-OHDA impairs the rats performance in the novel object discrimination task.•6-OHDA impairs the rats performance in the modified Y-maze task.•Memory deficits elicited by 6-OHDA are associated with mPFC dopaminergic alterations. 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.