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Loss and remodeling of striatal dendritic spines in Parkinson’s disease: from homeostasis to maladaptive plasticity?

  • Translational Neurosciences - Review Article
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Abstract

In Parkinson’s disease (PD) patients and animal models of PD, the progressive degeneration of the nigrostriatal dopamine (DA) projection leads to two major changes in the morphology of striatal projection neurons (SPNs), i.e., a profound loss of dendritic spines and the remodeling of axospinous glutamatergic synapses. Striatal spine loss is an early event tightly associated with the extent of striatal DA denervation, but not the severity of parkinsonian motor symptoms, suggesting that striatal spine pruning might be a form of homeostatic plasticity that compensates for the loss of striatal DA innervation and the resulting dysregulation of corticostriatal glutamatergic transmission. On the other hand, the remodeling of axospinous corticostriatal and thalamostriatal glutamatergic synapses might represent a form of late maladaptive plasticity that underlies changes in the strength and plastic properties of these afferents and the resulting increased firing and bursting activity of striatal SPNs in the parkinsonian state. There is also evidence that these abnormal synaptic connections might contribute to the pathophysiology of l-DOPA-induced dyskinesia. Despite the significant advances made in this field over the last thirty years, many controversial issues remain about the striatal SPN subtypes affected, the role of spine changes in the altered activity of SPNs in the parkinsonisn state, and the importance of striatal spine plasticity in the pathophysiology of l-DOPA-induced dyskinesia. In this review, we will examine the current state of knowledge of these issues, discuss the limitations of the animal models used to address some of these questions, and assess the relevance of data from animal models to the human-diseased condition.

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Acknowledgements

The authors thank Jean-Francois Pare and Susan Jenkins for their technical assistance. This work was supported by the NIH Grants R01NS083386 (YS) and P50NS098685 (YS) and the Yerkes Primate Center base Grant P51OD01113.

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Authors and Affiliations

  1. Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA, 30329, USA

    Rosa M. Villalba & Yoland Smith

  2. UDALL Center of Excellence for Parkinson’s Disease, Emory University, Atlanta, GA, USA

    Rosa M. Villalba & Yoland Smith

  3. Department of Neurology, Emory University, Atlanta, GA, USA

    Yoland Smith

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  1. Rosa M. Villalba
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Villalba, R.M., Smith, Y. Loss and remodeling of striatal dendritic spines in Parkinson’s disease: from homeostasis to maladaptive plasticity?. J Neural Transm 125, 431–447 (2018). https://doi.org/10.1007/s00702-017-1735-6

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