Behavioral associations of neuronal activity in the ventral tegmental area of the rat

Abstract

The ventral tegmental area (VTA) is a central element in a system that mediates the reinforcing properties of natural stimuli (such as food), brain stimulation, and drugs of abuse. Although considerable effort has been applied to understanding how drugs of abuse influence this system, relatively little work has examined its function during conditioned reinforcement tasks in awake, behaving animals. In the present studies, bundles of four to eight microwire electrodes were chronically implanted in the VTA or prefrontal cortex (PFC) of male Wistar rats. Following recovery from surgery, simultaneous recordings from multiple single neurons and unit clusters were obtained in rats pressing a lever for a sucrose solution on a fixed-ratio schedule of reinforcement. Consistent with the hypothesis that these neurons encode information related to motivation, most of the neurons in both VTA and PFC showed significant modulation of firing rate associated with one or more events occurring within the response/reinforcement cycle. These events included lever presses, onset and end of a tone signaling sucrose delivery, and onset and end of sucrose consumption. Significant decreases in firing rate were observed, coincident with onset of the tone and sucrose delivery, or with consumption. These decreases were sustained through the end of sucrose consumption. A number of neurons also discharged bursts of activity associated with individual lever presses. These findings provide a clear demonstration that VTA neuronal activity is modulated during motivated behavior. Similar information about events within the ongoing response/reinforcement cycle appears to be distributed through many neurons within the VTA, and may be mirrored in target structures such as PFC.

Dopamine Cells Respond to Predicted Events during Classical Conditioning: Evidence for Eligibility Traces in the Reward-Learning Network

“…These results extend previous findings from rats that DA cells respond to sensory cues predicting reward (Miller et al, 1981;Kosobud et al, 1994;Kiyatkin and Rebec, 2001;Hyland et al, 2002) and show for the first time that these are contingent on cue-reward association and arise during acquisition of classically conditioned behavior. We also noted significant depression of DA cell activity at the time of omitted rewards, indicating that rat Fig.…”

Behavioral significance of phasic changes in mesolimbic dopamine-dependent electrochemical signal associated with heroin self-injections

“…always occurred 10-12 min after heroin injection preceding the next lever-press for drug, and this activation was acutely blocked by heroin infusion, signal decreases may reflect the cessation of previous behavior-associated DA activation that correlates with powerful "sedation" developed immediately after heroin injection. Although there is no direct evidence for this mechanism, it should be noted that VTA DA cell activation has been seen in trained animals after presentation of food-related conditioned stimuli preceding the operant response for food, while subsequent food consumption was associated with the abrupt cessation of this activation (Kosobud et al, 1993;Nishino et al, 1987;Schultz, 1986;Schultz and Romo, 1990). Similarly, "anticipatory" increases in DA signal preceding the actual interaction with the reinforcer and relative signal decreases following interaction with the reinforcer were recently reported using electrochemistry in models of :feeding and sexual behavior (Phillips et al, 1991(Phillips et al, , 1993Kiyatkin and Gratton, in press).…”

Role of 5-HT2A and 5-HT2C/B receptors in the acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on striatal single-unit activity and locomotion in freely moving rats

“…To be classified as single-neuron activity, waveforms had to display a signal-to-noise ratio of at least 2.5:1 and exhibit consistent shape and amplitude. Analysis of autocorrelations also was used to support single-unit activity classification (Harris et al 2000;Kosobud et al 1994;Rieke et al 1997). Specifically, units that displayed a trough in the autocorrelation at t<10 ms were considered to be single-neuron recordings.…”