Long-term dopamine neurochemical monitoring in primates

• Main Authors: Shimazu, Hideki (Contributor), Amemori, Ken-ichi (Contributor), Amemori, Satoko (Contributor), Tierney, Patrick (Contributor), Hong, Simon (Contributor), Yoshida, Tomoko (Contributor), Langer, Robert S (Contributor), Graybiel, Ann M (Contributor), Cima, Michael J. (Author), Schwerdt, Helen (Author), Gibson, Daniel J. (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), Massachusetts Institute of Technology. Department of Chemical Engineering (Contributor), Massachusetts Institute of Technology. Department of Materials Science and Engineering (Contributor), McGovern Institute for Brain Research at MIT (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor), Schwerdt, Helen N (Contributor), Gibson, Daniel J (Contributor), Cima, Michael J (Contributor)
• Format: Article
• Language: English
• Published: National Academy of Sciences (U.S.), 2018-07-24T17:27:15Z.
• Subjects: Article
• Online Access: Get fulltext

Many debilitating neuropsychiatric and neurodegenerative disorders are characterized by dopamine neurotransmitter dysregulation. Monitoring subsecond dopamine release accurately and for extended, clinically relevant timescales is a critical unmet need. Especially valuable has been the development of electrochemical fast-scan cyclic voltammetry implementing microsized carbon fiber probe implants to record fast millisecond changes in dopamine concentrations. Nevertheless, these well-established methods have only been applied in primates with acutely (few hours) implanted sensors. Neurochemical monitoring for long timescales is necessary to improve diagnostic and therapeutic procedures for a wide range of neurological disorders. Strategies for the chronic use of such sensors have recently been established successfully in rodents, but new infrastructures are needed to enable these strategies in primates. Here we report an integrated neurochemical recording platform for monitoring dopamine release from sensors chronically implanted in deep brain structures of nonhuman primates for over 100 days, together with results for behavior-related and stimulation-induced dopamine release. From these chronically implanted probes, we measured dopamine release from multiple sites in the striatum as induced by behavioral performance and reward-related stimuli, by direct stimulation, and by drug administration. We further developed algorithms to automate detection of dopamine. These algorithms could be used to track the effects of drugs on endogenous dopamine neurotransmission, as well as to evaluate the long-term performance of the chronically implanted sensors. Our chronic measurements demonstrate the feasibility of measuring subsecond dopamine release from deep brain circuits of awake, behaving primates in a longitudinally reproducible manner. Keywords: striatum; voltammetry; neurotransmitters; chronic implants
National Institute of Neurological Diseases and Stroke (U.S.) (Grant R01 NS025529)
National Institute of Neurological Diseases and Stroke (U.S.) (Grant F32 NS093897)
United States. Army Research Office (Contract W911NF-16-1-0474)
National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101)