Spine Enlargement of Pyramidal Tract-Type Neurons in the Motor Cortex of a Rat Model of Levodopa-Induced Dyskinesia.

Tatsuya Ueno,Shinya Ueno,Haruo Nishijima,Masahiko Tomiyama

doi:10.3389/fnins.2017.00206

Tatsuya Ueno, Shinya Ueno + Show 2 more

Open Access

https://doi.org/10.3389/fnins.2017.00206

Copy DOI

Abstract

Growing evidence suggests that abnormal synaptic plasticity of cortical neurons underlies levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). Spine morphology reflects synaptic plasticity resulting from glutamatergic transmission. We previously reported that enlargement of the dendritic spines of intratelencephalic-type (IT) neurons in the primary motor cortex (M1) is linked to the development of LID. However, the relevance of another M1 neuron type, pyramidal-tract (PT) neurons, to LID remains unknown. We examined the morphological changes of the dendritic spines of M1 PT neurons in a rat model of LID. We quantified the density and size of these spines in 6-hydroxydopamine-lesioned rats (a model of PD), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Dopaminergic denervation alone had no effect on spine density and head area. However, the LID model showed significant increases in the density and spine head area and the development of dyskinetic movements. In contrast, levodopa treatment of normal rats increased spine density alone. Although, chronic levodopa treatment increases PT neuron spine density, with or without dopaminergic denervation, enlargement of PT neuron spines appears to be a specific feature of LID. This finding suggests that PT neurons become hyperexcited in the LID model, in parallel with the enlargement of spines. Thus, spine enlargement, and the resultant hyperexcitability of PT pyramidal neurons, in the M1 cortex might contribute to abnormal cortical neuronal plasticity in LID.

Highlights

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain, resulting in bradykinesia, muscular rigidity, rest tremor, and postural instability (Gibb and Lees, 1988)
Electrophysiological recordings performed in corticostriatal slices of 6-hydroxydopamine (6-OHDA) lesioned rats with levodopa-induced dyskinesia (LID) have shown that depotentiation at corticostriatal synapses to direct pathway striatal projection neurons is lost after the induction of long-term potentiation (LTP) (Shen et al, 2015)
Dopaminergic denervation plus levodopa treatment (LID group) significantly increased abnormal involuntary movement (AIM) scores at day 4 (P < 0.001 cf. day 1) and day 11 (P < 0.001 cf. day 4), whereas levodopa treatment had no effect on AIM scores in control rats (LTC group) (Figure 3)

Summary

Introduction

Parkinson’s disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra of the midbrain, resulting in bradykinesia, muscular rigidity, rest tremor, and postural instability (Gibb and Lees, 1988). Long-term treatment with levodopa induces a variety of abnormal involuntary movements, termed levodopa-induced dyskinesia (LID), which represent a major treatment limitation and reduce the quality of life of PD patients (Olanow et al, 2006). The emergence of these abnormal involuntary movements is associated with altered corticostriatal synaptic plasticity (Picconi et al, 2003). Electrophysiological recordings performed in corticostriatal slices of 6-hydroxydopamine (6-OHDA) lesioned rats with LID have shown that depotentiation at corticostriatal synapses to direct pathway striatal projection neurons (dSPN) is lost after the induction of long-term potentiation (LTP) (Shen et al, 2015). In a rat model of LID, we showed that dSPN dendritic spines became enlarged, suggesting supersensitivity of the corticostriatal excitatory synapses of dSPNs (Nishijima et al, 2014)

Methods

Results

Discussion

Conclusion