itive stimulation. However, a burst of
high-frequency stimulation can markedly
enhance the response to subsequent low-
frequency pulses, a change known as long-
(LTP) that can last for
a period of hours. LTP is widely consid-
ered to be a cellular model of learning. In
the striatum, LTP depends on activation
of striatal dopamine synapses, as it is
blocked by dopamine receptor blockade
and by lesions of the endogenous
that dopamine-dependent LTP was
restored in lesioned animals by chronic
treatment with low doses of
), whether or not the animals
Although establishing new associa-
tions is important, if learning is to be
adaptive, the ability to ‘forget’ or ‘ignore’
irrelevant associations is also key. One
mechanism for such regulation in LTP is
depotentiation, whereby several minutes
of low-frequency stimulation can abol-
ish the potentiation provided by the
high-frequency burst in the initial estab-
lishment of LTP (
). In the current
L-DOPA restored LTP,
including depotentiation, in the animals
that did not develop dyskinesia, depo-
tentiation was not induced in dyskinetic
induced dyskinesia is associated with
(and perhaps results from) abnormal
regulation of LTP in the striatum.
those that do not develop dyskinesias would
facilitate the identification of novel strate-
gies to maintain or restore normal physio-
logical plasticity in the striatum during
L-DOPA treatment and optimize the effica-
cy of the drug as a dyskinesia-free therapy
for Parkinson’s disease.
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