Front. Syst. Neurosci., 23 August 2011 |

Neuroglial plasticity at striatal glutamatergic synapses in Parkinson’s disease

  • 1 Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA
  • 2 Department of Neurology, Emory University, Atlanta, GA, USA

Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD). Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba and Smith, 2011). The concept of tripartite synapses (TS) was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a). Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia–neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD therapeutics.

Keywords: glia, MPTP, non-human primates, tripartite synapses, astrocyte, striatum, corticostriatal, thalamostriatal

Citation: Villalba RM and Smith Y (2011) Neuroglial plasticity at striatal glutamatergic synapses in Parkinson’s disease. Front. Syst. Neurosci. 5:68. doi: 10.3389/fnsys.2011.00068

Received: 22 April 2011; Paper pending published: 12 May 2011;
Accepted: 02 August 2011; Published online: 23 August 2011.

Edited by:

James M. Tepper, Rutgers, The State University of New Jersey, USA

Reviewed by:

Jose L. Lanciego, University of Navarra, Spain
Paul Bolam, University of Oxford, UK

Copyright: © 2011 Villalba and Smith. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.

*Correspondence: Rosa M. Villalba, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA. e-mail: