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

Filipe C. Matheus, Daniel Rial, Joana I. Real, Cristina Lemos, Juliana Ben, Gisele O. Guaita, Inês R. Pita, Ana C. Sequeira, Frederico C. Pereira, Roger Walz, Reinaldo N. Takahashi, Leandro J. Bertoglio, Cláudio Da Cunha, Rodrigo A. Cunha, Rui D. Prediger
Behavioural Brain Research. 2016-03-01; 301: 43-54
DOI: 10.1016/j.bbr.2015.12.011

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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.


Auteurs Bordeaux Neurocampus