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

J Neural Transm (Vienna). 2018 Mar;125(3):431-447. doi: 10.1007/s00702-017-1735-6. Epub 2017 May 24.


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.

Keywords: Corticostriatal; Dopamine; Glutamate; Monkey; Striatum; Thalamostriatal.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Corpus Striatum / pathology*
  • Corpus Striatum / physiopathology
  • Dendritic Spines / pathology*
  • Disease Models, Animal
  • Haplorhini
  • Homeostasis / physiology*
  • Neuronal Plasticity / physiology*
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology