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.
Highlights
The dopamine (DA) projection of the brain originates from the ventral tegmental area (VTA), substantia nigra pars compacta (SNc) and retrorubral area (RRA) [1], and projects to broad swaths of cortex and basal ganglia [2,3], with a smaller presence in the cerebellum [4,5]
We carried out experiments in which a stimulation electrode was introduced into the VTA/SNc and a carbon fiber electrode was introduced into the ventral striatum
VTA/SNc evoked dopamine oxidation peaks in the brain were higher than oxidation peaks recorded in the flow cell, typically by about 160 mV
Summary
The dopamine (DA) projection of the brain originates from the ventral tegmental area (VTA), substantia nigra pars compacta (SNc) and retrorubral area (RRA) [1], and projects to broad swaths of cortex and basal ganglia [2,3], with a smaller presence in the cerebellum [4,5]. The effects of rodent MFB stimulation were traced to VTA neurons and DA release through a series of pharmacological, anatomical and electrophysiological studies (see [7]). FSCV is an electrochemical technique for measuring the concentration of an electrolyte in solution using a wide bandwidth two-electrode sweeping voltage clamp. This technique has been extensively developed in rodents [11] where a thin (e.g., 7 mm) strand of carbon fiber is used as the working electrode. FSCV has important advantages over other in vivo techniques for measuring DA concentration because of its ionic specificity, and its temporal and spatial resolutions. Data from FSCV provides localized real-time phasic characteristics that can capture DA release, diffusion and clearance
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