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 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.
Established in 1930, the Yerkes National Primate Research Center paved the way for what has become the National Institutes of Health-funded National Primate Research Center (NPRC) program. For more than eight decades, the Yerkes Research Center has been dedicated to conducting essential basic science and translational research to advance scientific understanding and to improve human health and well-being. Today, the Yerkes Research Center is one of only eight NPRCs. The center provides leadership, training and resources to foster scientific creativity, collaboration and discoveries, and research at the center is grounded in scientific integrity, expert knowledge, respect for colleagues, an open exchange of ideas and compassionate, quality animal care.
In the fields of microbiology and immunology, infectious diseases, pharmacology and drug discovery, transplantation, neurologic and psychiatric diseases, as well as behavioral, cognitive and developmental neuroscience, Yerkes scientists use innovative experimental models and cutting-edge technologies to explore and test transformative concepts aimed at: preventing and treating viral diseases such as AIDS; designing novel vaccines for infectious diseases such as malaria and tuberculosis; enhancing the potential of organ transplantation and regenerative medicine; discovering new drugs and drug classes through high-throughput screening; defining the basic neurobiology and genetics of social behavior and developing new therapies for disorders such as autism and drug addiction; understanding the biology of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases; and advancing knowledge about the evolutionary links between biology and behavior.