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

Arun Singh, Klaus Mewes, Robert E. Gross, Mahlon R. DeLong, José A. Obeso, Stella M. Papa

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9629-9634
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number34
DOIs
StatePublished - Aug 23 2016

Bibliographical note

Funding Information:
This study was supported by NIH Grants NS045962 and NS073994, National Center for Research Resources RR000165, Office of Research Infrastructure Programs/Office of the Director OD011132 (to S.M.P.), SAF2012-40216 and SAF2015-67239-P Plan Nacional, Ministerio de Econom?a y Competitividad (to J.A.O.), and American Parkinson's Disease Association Advanced Center for Research (M.R.D. and K.M.).

Keywords

  • Basal ganglia
  • Dopamine
  • Electrophysiology
  • Parkinson's disease
  • Striatal projection neuron

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