Dopamine-dependent long-term depression at subthalamo-nigral synapses is lost in experimental parkinsonism
Journal of Neuroscience. 2013-09-04; 33(36): 14331-14341
DOI: 10.1523/JNEUROSCI.1681-13.2013
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1. J Neurosci. 2013 Sep 4;33(36):14331-41. doi: 10.1523/JNEUROSCI.1681-13.2013.
Dopamine-dependent long-term depression at subthalamo-nigral synapses is lost in
experimental parkinsonism.
Dupuis JP(1), Feyder M, Miguelez C, Garcia L, Morin S, Choquet D, Hosy E, Bezard
E, Fisone G, Bioulac BH, Baufreton J.
Author information:
(1)Université Bordeaux and Centre National de la Recherche Scientifique, Institut
des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
Impairments of synaptic plasticity are a hallmark of several neurological
disorders, including Parkinson’s disease (PD) which results from the progressive
loss of dopaminergic neurons of the substantia nigra pars compacta leading to
abnormal activity within the basal ganglia (BG) network and pathological motor
symptoms. Indeed, disrupted plasticity at corticostriatal glutamatergic synapses,
the gateway of the BG, is correlated to the onset of PD-related movement
disorders and thus has been proposed to be a key neural substrate regulating
information flow and motor function in BG circuits. However, a critical question
is whether similar plasticity impairments could occur at other glutamatergic
connections within the BG that would also affect the inhibitory influence of the
network on the motor thalamus. Here, we show that long-term plasticity at
subthalamo-nigral glutamatergic synapses (STN-SNr) sculpting the activity
patterns of nigral neurons, the main output of the network, is also affected in
experimental parkinsonism. Using whole-cell patch-clamp in acute rat brain
slices, we describe a molecular pathway supporting an activity-dependent
long-term depression of STN-SNr synapses through an NMDAR-and D1/5 dopamine
receptor-mediated endocytosis of synaptic AMPA glutamate receptors. We also show
that this plastic property is lost in an experimental rat model of PD but can be
restored through the recruitment of dopamine D1/5 receptors. Altogether, our
findings suggest that pathological impairments of subthalamo-nigral plasticity
may enhance BG outputs and thereby contribute to PD-related motor dysfunctions.
DOI: 10.1523/JNEUROSCI.1681-13.2013
PMID: 24005286 [Indexed for MEDLINE]