The Robinson Lab studies brain mechanisms during alcohol drinking in rats with the aim to understand neuronal circuitry underlying alcohol-motivated behavior. We primarily make two kinds of measurements: electrophysiological and electrochemical. With electrophysiology, we use a voltage follower to monitor action potentials of nucleus accumbens neurons, detected at chronically implanted microelectrode arrays (Figure 1).
Figure 1. Electrophysiological waveforms of medium spiny neurons in the nucleus accumbens. The three waveforms were detected on a single microwire electrode and differentiated using principal component analysis.
With electrochemistry, we use a current follower to monitor fluctuations in dopamine concentrations on a subsecond timescale, by using fast scan cyclic voltammetry at acutely implanted carbon fiber microelectrodes (Figure 2). Together these techniques offer a window on information processing in the nucleus accumbens while rats press levers for alcohol or other reinforcers. After establishing baseline neuronal activity, we can test the effects of experimental manipulations (homeostatic drives, therapeutic drugs, alcohol dependence) on the neuronal measurements.
Figure 2.Dopamine transients in the nucleus accumbens after intravenous administration of 2 g/kg ethanol. A: Changes in current are confirmed to be due to oxidation of dopamine by statistical inspection of the cyclic voltammogram, which shows a characteristic oxidative peak at ~600 mV and reductive peak at ~200 mV versus the Ag/AgCl reference. B: The current versus time trace at the oxidation potential of dopamine is converted to concentration by using in vitro postcalibration of the electrode. Dopamine transients are marked with asterisks. C: The electrochemical information across time is represented in a color plot of applied potential on the y-axis, time on the x-axis and current in false color.
Figure 3: Below is a 12-s video of a rat self-administering alcohol. On the bottom of the screen, the dopamine signal from the ventral striatum of that rat scrolls on in real-time with the video. At first, the lever is retracted and the rat turns back and forth from the lever to the empty cup. But when the lights change, the lever extends and the rat immediately presses it -- this event is accompanied by a dopamine transient (~ 70 nM), and the rat turns to drink the alcohol. (The following video requires Flash)
Bowles Center for Alcohol Studies at the University of North Carolina at Chapel Hill