Summary: Researchers have successfully recorded neural activity in the human striatum.
Source: Emory Health Sciences.
Researchers at Yerkes National Primate Research Center, Emory University, are the first to systematically record neural activity in the human striatum, a deep brain structure that plays a major role in cognitive and motor function. These two functions are compromised in Parkinson’s disease (PD), which makes the neuron-firing abnormalities the study results revealed key to better understanding the pathophysiology of PD and, ultimately, developing better treatments and preventions. The study findings are reported in the current online issue of the Proceedings of the National Academy of Sciences.
Nearly one million people in the U.S. are living with PD, a chronic and progressive neurodegenerative disorder.
In this study, the Yerkes researchers compared striatal recordings across people who have PD and other neurological disorders (dystonia and essential tremor) with correlative findings in nonhuman primates. The researchers undertook a rigorous, several-year selection process to find the right patients undergoing surgical deep brain stimulation treatment in order to obtain sufficient recordings. The study was further supported by the researchers comparing data obtained in nonhuman primates, which provided critical animal controls and disease models.
“We found profound changes in the activity of striatal projection neurons in patients with PD, which highlighted the striatal role in circuit dysfunction” says Stella Papa, MD, lead researcher for this study. According to Dr. Papa, until now, basal ganglia circuit models of PD have been based on presumptive changes in the outputs of the dopamine-depleted striatum that were never found in human studies. “The data we are providing in this new study have long been due and weigh significantly in the interpretation of striatal mechanisms in basal ganglia circuits and their contribution to the pathophysiology of PD,” she continues.
The researchers next steps are to continue investigating the physiological and molecular mechanisms participating in the abnormal firing of striatal projection neurons in PD. Understanding these mechanisms is key to developing target-specific treatments to improve the lives of people who have PD.
Funding: Funding for this research was supported by the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke Grants NS045962 and NS073994, the NIH Office of Research Infrastructure Programs (Yerkes National Primate Research Center – P51OD011132), SAF2012-40216 and SAF2015-67239-P Plan Nacional, Ministerio de Economía y Competitividad and the American Parkinson’s Disease Association Advanced Center for Research.
Source: Lisa Newbern – Emory Health Sciences
Image Source: This NeuroscienceNews.com image is credited to Bruttokolliko, licensed CC BY SA 4.0.
Original Research: Abstract for “Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson’s disease” by Arun Singh, Klaus Mewes, Robert E. Gross, Mahlon R. DeLong, José A. Obeso, and Stella M. Papa in PNAS. Published online August 8 2016 doi:10.1073/pnas.1606792113
Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson’s disease
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.
“Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson’s disease” by Arun Singh, Klaus Mewes, Robert E. Gross, Mahlon R. DeLong, José A. Obeso, and Stella M. Papa in PNAS. Published online August 8 2016 doi:10.1073/pnas.1606792113