Ventral Pallidum Plays Active Role in Reward-Seeking Behavior

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Pharmacological and optogenetic inhibition of ventral pallidum neurons during cue presentation impedes reward-seeking behavior.
Pharmacological and optogenetic inhibition of ventral pallidum neurons during cue presentation impedes reward-seeking behavior.

The ventral pallidum (VP) was first recognized as a distinct anatomical structure in 1975, when it was identified as the primary output for the ventral striatum.1 According to the accepted view, the VP is a relay for ‘indirect' pathway signals from the nucleus accumbens (NAc), “which in the dorsal striatum are primarily carried by D2-dopamine receptor-expressing medium spiny neurons (D2 MSNs),” wrote the authors of a new study published in Neuron.2 “Yet, emerging research suggests that this segregation of D1 ‘direct' and D2 ‘indirect' output pathways does not apply to the ventral basal ganglia…, where similar proportions of D1 and D2 MSNs project from NAc to VP…and are equally likely to target VP neurons that project to the thalamus,” they explained.

Previous findings have implicated both the VP and the NAc in the promotion of cue-evoked reward-seeking actions. Cue-elicited responses in NAc neurons were shown to encode cue value, as well as the “probability and vigor of reward-seeking actions” in a discriminative stimulus (DS) task, whereas VP neurons have been found to encode the cue value of primary and Pavlovian rewards. However, the link between VP neuron responses and reward-seeking actions has not been explored. The authors of the current study examined the role of VP neurons in a DS task, and they further investigated how these neurons encode a DS, how their responses compare to NAc neuron responses, and whether they predict the vigor of reward-seeking actions.

For the first part of the experiment, rats were trained to perform a task in which the DS was an auditory cue with a duration of up to 10 seconds. When the rats pressed a lever while the DS was being presented – vs when the DS was not present or when an alternate cue was being presented – they received a highly preferred reward of 10% liquid sucrose. To assess whether VP neuron activity is necessary for performance of the DS task, the researchers inactivated the VP of some of the rats with “a low-dose mixture of the GABAA agonist muscimol and the GABAB agonist baclofen,” they wrote. While this manipulation had no effect on total active presses (t(6) = 0.9702, p = 0.0536), it did reduce the probability of a DS response (t(6) = 3.087, p = 0.0215), with 3 of 7 rats making zero responses after VP inactivation. This finding establishes the necessity of VP activity in DS task performance.

The authors then trained the rats to achieve particular task response ratios and implanted them with multielectrode arrays aimed at the VP. The findings indicate that the “onset of VP neuron responses occurs at a shorter latency than cue-elicited responses in NAc neurons,” contrary to expectation, and that “VP neurons encode both learned cue value and subsequent reward seeking,” they reported. Taken together, these results establish the critical role of VP neuron activity in generating reward-seeking behaviors, indicating that “VP encoding is not a passive response to signals generated in the NAc and that VP neurons integrate sensory and motivation-related information received directly from other mesocorticolimbic inputs,” the authors noted.

The researchers also used optogenetic tools to inhibit VP neuron activity while the DS was being presented. In line with their previous observations, inhibition of VP during the DS significantly increased both latency to level press (F(1,11) = 10.615, p = 0.008) and number of omissions (F(1,11) = 6.672, p = 0.025). This “indicates that VP activity during the cue actively promotes DS-elicited reward seeking behavior,” the authors concluded.

References

1. Smith KS, Tindell AJ, Aldridge JW, Berridge KC. Ventral pallidum roles in reward and motivation. Behav Brain Res. 2009; 196(2): 155–167.

2. Richard JM, Ambroggi F, Janak PH, Fields HL Ventral pallidum neurons encode incentive value and promote cue-elicited instrumental actions. Neuron. 2016; doi: 10.1016/j.neuron.2016.04.037.

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