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