Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease

Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9629-34. doi: 10.1073/pnas.1606792113. Epub 2016 Aug 8.

Abstract

Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

Keywords: Parkinson’s disease; basal ganglia; dopamine; electrophysiology; striatal projection neuron.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Action Potentials*
  • Aged
  • Aged, 80 and over
  • Animals
  • Basal Ganglia / metabolism
  • Basal Ganglia / physiopathology
  • Corpus Striatum / metabolism
  • Corpus Striatum / physiopathology*
  • Deep Brain Stimulation
  • Dopamine / metabolism
  • Dystonia / metabolism
  • Dystonia / physiopathology*
  • Dystonia / therapy
  • Essential Tremor / metabolism
  • Essential Tremor / physiopathology*
  • Essential Tremor / therapy
  • Female
  • Humans
  • Macaca mulatta
  • Male
  • Middle Aged
  • Parkinson Disease / metabolism
  • Parkinson Disease / physiopathology*
  • Parkinson Disease / therapy
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / metabolism
  • Parkinson Disease, Secondary / physiopathology*
  • Parkinson Disease, Secondary / therapy

Substances

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine