While recording VTA DA neuronal activity, the animal was presented a series of 50 or 100 auditory stimuli (1 ms, 73 dB) and the same number of visual stimuli (light flashes, 1.5 X 106 candle power, 1.9 X 107 lumens peak intensity) with a randomly varied interstimulus interval of 10-30 s.

Fig. 1: Response of an individual ventral tegmental dopamine neuron to 50 presentations of a 1 ms auditory click (left panel) and 50 presentations of a light flash (right panel) {from Horvitz, Stewart, and Jacobs, Brain Research, 759, 251-258, 1997}

Auditory responses were observed in 13 of 15 ventral tegmental DA neurons (87%), visual responses were observed in 9 of 12 DA cells (75%). Auditory and visual responses appeared identical with the exception that the latency to peak visual response was longer than that of the auditory response (p<.01).

Fig. 2: Mean probability of VTA DA neuronal firing from 400 ms before to 600 ms after the delivery of an auditory (top) or visual (bottom) stimulus (arrow). Probability estimates, at each time bin, were averaged across all DA neurons tested for an auditory or visual response. Asterisks mark the poststimulus time bins for each neuronal discharge for which discharge probability was significantly greater than that observed during the prestimulus baseline (*P<0.05, **P<0.01). From Horvitz et al., 1997.

VTA DA response to auditory stimuli of varying intensities. Animals received 20 presentations of the 1 ms auditory event at each of the following intensities: 58, 66, 73, and 80 dB. The 4 different intensities were presented randomly (without replacement).

Increasing auditory intensity increased the likelihood of an action potential occurring between 0-150 ms after presentation of the auditory event (p < 0.01). Increased auditory intensities increased the likelihood of a dopamine burst response during a given trial (p< 0.01), but did not affect the duration of burst firing.

VTA DA response to a auditory stimulus signaling reward delivery.

A 1 ms click (73 dB) was followed, 1 sec later, by milk delivery, with a variable inter-trial interval of 15-60 sec.

Fig. 3:The response of an individual VTA DA neuron is shown 400 ms before to 600 ms after presentation of a 1 ms click (arrow). The DA response to the auditory event is shown prior to classical click/milk pairings (top left, "click"), during CS/US conditioning (top right, "click signals reward"), during extinction, i.e., click alone (bottom left, "click"), and during re-establishment of the CS/US association (bottom right, "click signals reward").

As seen in the previous sensory tests, DA neurons were responsive to this fast rise-time, high-intensity auditory event even before it was paired with reward (top left). The DA response to the click was enhanced after it had come to predict reward delivery (top right). After conditioning, (bottom left) the DA response resembled that seen prior to conditioning. Reacquisition of the click/milk association (bottom right) reinstated the enhanced VTA DA neuronal response. After the click had become a conditioned signal for reward, it produced a VTA DA response that was elevated for several hundred ms beyond that seen when the same stimulus was not a predictor of reward. Only a small number (n=5) VTA DA neurons were subjected to this conditioned reward test, and conditioned elevations in burst duration were seen in 3 of the 5 cells, with the other cells unresponsive to the auditory event. It is of interest to note that while the DA neuronal response increased in duration when the click signaled imminent reward delivery, increases in auditory stimulus intensity elevated the likelihood of a DA neuronal burst response, but did not increase duration of the DA response.

Conclusion

DA neurons responded to nonconditioned, non-appetitive auditory and visual events. The DA response was elevated by a) increasing stimulus intensity and b) leaving intensity constant and pairing the event with an important outcome (milk delivery). The increase in stimulus intensity increased the likelihood of occurrence of a DA action potential in response to a given presentation of the sensory event, while pairing the event with reward also increased the duration of the neuronal response. One could argue that the VTA DA neuron transmits a signal of reward or conditioned reward by virtue of its sustained versus short duration response. However, it seems likely instead that the DA neuron responds to salient sensory events regardless of whether the salience is due to physical intensity or conditioned properties of the event. These DA elevations in response to salient events may serve to promote processing of afferent signals simultaneously arriving at the accumbens and other mesolimbic DA target structures.

References

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Horvitz, J.C., Stewart, T., and Jacobs, B.L., 1997, Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat, Brain Research, 759, 251-258.

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