Abstract
The emergence of L-DOPA-induced dyskinesia (LID) in patients with Parkinson disease (PD) could be due to maladaptive plasticity of corticostriatal synapses in response to L-DOPA treatment. A series of recent studies has revealed that LID is associated with marked morphological plasticity of striatal dendritic spines, particularly cell type-specific structural plasticity of medium spiny neurons (MSNs) in the striatum. In addition, evidence demonstrating the occurrence of plastic adaptations, including aberrant morphological and functional features, in multiple components of cortico-basal ganglionic circuitry, such as primary motor cortex (M1) and basal ganglia (BG) output nuclei. These adaptations have been implicated in the pathophysiology of LID. Here, we briefly review recent studies that have addressed maladaptive plastic changes within the cortico-BG loop in dyskinetic animal models of PD and patients with PD.
Highlights
Edited by: Kuan Hong Wang, National Institute of Mental Health, NIH, USAReviewed by: Xin Jin, Salk Institute for Biological Studies, USADivya Sitaraman, University of San Diego, USAReceived: 17 February 2016 Accepted: 05 December 2016 Published: 20 December 2016Citation: Wang Q and Zhang W (2016) Maladaptive Synaptic Plasticity in L-DOPA-InducedDyskinesia
Parkinson’s disease (PD) is characterized by severe, progressive degeneration of nigrostriatal dopamine (DA) neurons, which results in motor deficits, including akinesia, rigidity, tremor and postural dysfunction
Several lines of evidence indicate that abnormal activation of protein kinase A (PKA)-mediated phosphorylation of dopamine- and cAMP-regulated phosphoprotein (DARPP)-32 at T34 (Picconi et al, 2003; Santini et al, 2007; Lebel et al, 2010) and PKA dependent phosphorylation of GluA1 at Ser845 (Santini et al, 2007, 2010) in dyskinesia may have profound repercussions on synaptic plasticity (Figure 1)
Summary
Received: 17 February 2016 Accepted: 05 December 2016 Published: 20 December 2016. Citation: Wang Q and Zhang W (2016) Maladaptive Synaptic Plasticity in L-DOPA-Induced. In striatal MSNs, D1Rs co-localize with NMDARs and form heteromeric complexes on dendritic spines (Fiorentini et al, 2006; Calabresi et al, 2010) These D1R/NMDAR complexes facilitate rapid trafficking of NMDAR subunits and modulate the potentiation of NMDAR responses, giving rise to activity-dependent synaptic plasticity changes that involve PKA and dopamine- and cAMP-regulated phosphoprotein (DARPP)-32-regulated phosphorylation of the NR1 subunits of NMDARs (Fiorentini et al, 2008; Murphy et al, 2014). Increased Gαolf levels has been associated with LID both unilateral lesion mice model (Alcacer et al, 2012) and PD patients who had received a chronic L-dopa treatment (Corvol et al, 2004) Another signaling component leading to the abnormal D1R-mediated transmission involved in LID is the adenylyl cyclase type 5 (AC5), which is highly expressed in striatal
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