Striatal plasticity and medium spiny neuron dendritic remodeling in parkinsonism

https://doi.org/10.1016/S1353-8020(08)70012-9Get rights and content

Abstract

Current approaches to Parkinson's Disease (PD) are largely based on our current understanding of the mechanisms that contribute to the death of nigrostriatal dopamine neurons. However, our understanding of the consequences of the loss of dopamine on the striatal target cells of nigrostriatal neurons is much less advanced. In particular, the compensatory changes that occur in striatal medium spiny neurons (MSNs) that have lost their normal dopamine input remains poorly understood. The compensatory changes may have either positive or negative effects. Among the alterations that occur in striatal cells of the dopamine-denervated striatum are dystrophic changes in the dendrites of MSNs, with a loss of dendritic length and dendritic spine number. Dendritic spines are the targets of convergent nigrostriatal dopamine and corticostriatal glutamate axons, and integrate these convergent signals to determine the nature of striatal output. The loss of these spines in the dopamine-denervated state may protect the MSN from overt excitotoxic death, but at the price of compromising MSN function. The loss of dendritic spines is thought be responsible for the gradual decrease in levodopa efficacy in late-stage PD, suggesting that therapeutic interventions need to be developed that target key downstream signaling complexes in medium spiny neurons.

References (46)

  • Z Wang et al.

    Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons

    Neuron

    (2006)
  • C Hansel et al.

    alphaCaMKII is essential for cerebellar LTD and motor learning

    Neuron

    (2006)
  • C Cepeda et al.

    Facilitated glutamatergic transmission in the striatum of D2 dopamine receptor-deficient mice

    J Neurophysiol

    (1998)
  • M Day et al.

    Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models

    Nat Neurosci

    (2006)
  • F Crick

    Do spines twitch?

    Trends Neurosci

    (1984)
  • J DeFelipe

    Brain plasticity and mental processes: Cajal again

    Nat Rev Neurosci

    (2006)
  • S Zaja-Milatovic et al.

    Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease

    Neurol

    (2005)
  • JJ Rodriguez et al.

    Enhancement of N-methyl-D-aspartate (NMDA) immunoreactivity in residual dendritic spines in the caudateputamen nucleus after chronic haloperidol administration

    Synapse

    (1999)
  • NS Bamford et al.

    Dopamine modulates release from corticostriatal terminals

    J Neurosci

    (2004)
  • Neely MD, Schmidt DE, Deutch AY. Cortical regulation of dopamine depletion-induced dendritic spine loss in striatal...
  • Segal M. Dendritic spines for neuroprotection: a hypothesis Trends Neurosci 1005;...
  • S Hernandez-Lopez et al.

    D2 dopamine receptors in striatal medium spiny neurons reduce L-type Ca2+ currents and excitability via a novel PLC[beta]1-IP3-calcineurin-signaling cascade

    Neurosci

    (2000)
  • Z Xia et al.

    The role of calmodulin as a signal integrator for synaptic plasticity

    Nat Rev Neurosci

    (2005)
  • Cited by (0)

    View full text