Real-Time Dopamine Measurement in Awake Monkeys

Abstract

Fast-scan cyclic voltammetry (FSCV) is often used to measure real-time dopamine (DA) concentrations in awake, behaving rodents. Extending this technique to work in monkeys would provide a platform for advanced behavioral studies and a primate model for preclinical research. The present study demonstrates the feasibility of DA recordings in two awake monkeys (Macaca mulatta) using a mixture of techniques adapted from rodent, primate and brain slice work. We developed a long carbon fiber electrode to operate in the larger primate brain. This electrode was lowered into the striatum each day using a recording chamber and a detachable micromanipulator system. A manipulator also moved one or more tungsten stimulating electrodes into either the nearby striatum or the ventral tegmental area/substantia nigra pars compacta (VTA/SNc). We developed an electrical stimulation controller to reduce artifacts during electrical stimulation. We also introduce a stimulation-based methodology for estimating distances between electrodes in the brain. Dopamine responses within the striatum were evoked by either stimulation of the striatum near the FSCV electrode, or stimulation within the VTA/SNc. Unexpected juice rewards also evoked dopamine responses in the ventral striatum. Thus, we demonstrate that robust dopamine responses can be recorded from awake, behaving primates with FSCV. In addition, we describe how a stimulation technique borrowed from the neuroprosthetics field can activate the distributed monkey midbrain dopamine system in a way that mimics rodent VTA stimulation.

Electrochemical Analysis of Neurotransmitters

“…However, local terminal stimulation, a technique regularly used in brain-slice studies, elicited dopamine release in 10 out of 14 attempts and facilitated the recording of dopamine release during an unexpected juice reward. Thus, in agreement with our published work in monkeys, Schluter et al (144) concluded that dopamine release is more difficult to detect in the primate brain than in rodents.…”

“…A more recent FSCV study by Schluter and coworkers (144) explored the use of electrical stimulation to evoke dopamine release in the rhesus striatum. Electrical stimulation of midbrain dopamine neurons in the substantia nigra/ventral tegmental area (SN/VTA) is widely used in rodent studies as an aid in electrode positioning and to study the regulation of dopamine overflow.…”

Subcellular probes for neurochemical recording from multiple brain sites

“…CFM sensors have realized prevalent implementation in analyzing the mechanisms of dopamine signaling and its function in our everyday behavior and in pathology 10,17–19 . Considerable studies have further attempted to investigate the spatial diversity of dopamine neurotransmission in the striatum using the CFM sensor 3,4,17,20,21 . These single channel investigations, however, are limited by the inability to reproduce precisely dopamine measurements at specific brain sites, as they require serial repositioning of the sensor and/or impractical numbers of specimens to assess dopamine heterogeneity.…”

Sampling Phasic Dopamine Signaling with Fast‐Scan Cyclic Voltammetry in Awake, Behaving Rats

“…Excellent review papers are available which thoroughly describe how the approach has been used in awake and behaving rats (Stamford, 1990; Phillips et al, 2003a; Robinson et al, 2003). The technique has also been used in other species including Drosophila (Vickrey et al, 2009), lamprey (Ryczko et al, 2013), mice (Parker et al, 2010; Natori et al, 2009; Ehrich et al, 2014), monkeys (Ariansen et al, 2012; Schluter et al, 2014), and humans (Kishida et al, 2011). …”