Opposing Regulation of Cocaine Seeking by Glutamate and GABA Neurons in the Ventral Pallidum

Heinsbroek, Jasper A.; Bobadilla, Ana-Clara; Dereschewitz, Eric; Assali, Ahlem; Chalhoub, Reda M; Cowan, Christopher W.; Kalivas, Peter W.

doi:10.1016/j.celrep.2020.01.023

Cited by 72 publications

(85 citation statements)

References 47 publications

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“…Nevertheless, consistent with previous in vivo electrophysiology studies (17,38), we saw little evidence for spatially distinct differences in reward encoding; more systematic and precise approaches are necessary to confirm the presence or absence of regional differences. There is also a growing literature on the roles of different cell types in VP in motivated behavior, especially the opposing roles of glutamatergic and GABAergic populations (14,32,33,39). Given the evidence that GABAergic neurons make up the majority of the VP population and that they positively encode value and promote reward-seeking behavior, we speculate that the outcome × time neurons we describe here are GABAergic.…”

Section: Discussionmentioning

confidence: 73%

Reward activity in ventral pallidum tracks satiety-sensitive preference and drives choice behavior

et al. 2020

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A key function of the nervous system is producing adaptive behavior across changing conditions, like physiological state. Although states like thirst and hunger are known to impact decision-making, the neurobiology of this phenomenon has been studied minimally. Here, we tracked evolving preference for sucrose and water as rats proceeded from a thirsty to sated state. As rats shifted from water choices to sucrose choices across the session, the activity of a majority of neurons in the ventral pallidum, a region crucial for reward-related behaviors, closely matched the evolving behavioral preference. The timing of this signal followed the pattern of a reward prediction error, occurring at the cue or the reward depending on when reward identity was revealed. Additionally, optogenetic stimulation of ventral pallidum neurons at the time of reward was able to reverse behavioral preference. Our results suggest that ventral pallidum neurons guide reward-related decisions across changing physiological states.

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Section: Discussionmentioning

confidence: 73%

Reward activity in ventral pallidum tracks satiety-sensitive preference and drives choice behavior

et al. 2020

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“…Due to less than 3% colocalization of D 1 R-and D 2 R-expressing fibers in the VP [39], we hypothesize that NAc D 1 R and D 2 R neurons each project to distinct targets in the VP. Indeed, a recent study showed that VP GABAergic neurons receive equal inputs from NAc D 1 R and D 2 R neurons [26]. However, NAc D 2 R neurons may specifically target VP wake-promoting neurons (e.g., wake-promoting GABAergic projection neurons), whereas NAc D 1 R neurons may specifically target VP GABAergic interneurons.…”

Section: Discussionmentioning

confidence: 99%

“…VP GABAergic neurons form monosynaptic connections with both VTA dopaminergic and GABAergic neurons VP GABAergic neurons send inhibitory inputs to the VTA [6,26]; however, chemogenetic activation of VP GABAergic neurons and optogenetic activation of VP GABA - VTA projections in vivo increased VTA TH+ neuronal activity, as demonstrated by c-Fos staining. In order to further explore the circuit mechanism of VP GABAergic neurons in regulating arousal, we injected the AAV 10 -hSyn-DIO-ChR2-mCherry construct into the VP of Vgat-Cre: GAD67-GFP double-transgenic mice and subsequently recorded activity of VTA neurons under blue-light stimulation in acute slices in vitro ( Supplementary Fig.…”

Section: Vp Gabaergic Neurons Regulate Arousal Through the Vta Pathwaymentioning

confidence: 99%

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

Luo

et al. 2020

Mol Psychiatry

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The ventral pallidum (VP) regulates motivation, drug addiction, and several behaviors that rely on heightened arousal. However, the role and underlying neural circuits of the VP in the control of wakefulness remain poorly understood. In the present study, we sought to elucidate the specific role of VP GABAergic neurons in controlling sleep–wake behaviors in mice. Fiber photometry revealed that the population activity of VP GABAergic neurons was increased during physiological transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep. Moreover, chemogenetic and optogenetic manipulations were leveraged to investigate a potential causal role of VP GABAergic neurons in initiating and/or maintaining arousal. In vivo optogenetic stimulation of VP GABAergic neurons innervating the ventral tegmental area (VTA) strongly promoted arousal via disinhibition of VTA dopaminergic neurons. Functional in vitro mapping revealed that VP GABAergic neurons, in principle, inhibited VTA GABAergic neurons but also inhibited VTA dopaminergic neurons. In addition, optogenetic stimulation of terminals of VP GABAergic neurons revealed that they promoted arousal by innervating the lateral hypothalamus, but not the mediodorsal thalamus or lateral habenula. The increased wakefulness chemogenetically evoked by VP GABAergic neuronal activation was completely abolished by pretreatment with dopaminergic D1 and D2/D3 receptor antagonists. Furthermore, activation of VP GABAergic neurons increased exploration time in both the open-field and light–dark box tests but did not modulate depression-like behaviors or food intake. Finally, chemogenetic inhibition of VP GABAergic neurons decreased arousal. Taken together, our findings indicate that VP GABAergic neurons are essential for arousal related to motivation.

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“…Finally, although these roles for the VP in stress and aversion have been identified in alcohol and other drug free animals, there is emerging evidence that drug withdrawal profoundly alters neurotransmission in the VP cell types (e.g. vGlut2) essential for aversion processing (Heinsbroek et al, 2020; Inbar et al, 2020).…”

Section: Vp and Aversive Motivationmentioning

confidence: 99%

The ventral pallidum and relapse in alcohol seeking

Prasad

McNally

2020

British J Pharmacology

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Alcohol‐use disorders are chronically relapsing conditions characterized by cycles of use, abstinence and relapse. The ventral pallidum (VP) is a key node in the neural circuits controlling relapse to alcohol seeking and a key target of pharmacotherapies for relapse prevention. There has been a significant increase in our understanding of the molecular, anatomical, pharmacological and functional properties of the ventral pallidum, laying foundations for a new understanding of its role in relapse to alcohol seeking and motivation. Here we review these advances, placing special emphasis on how advances in understanding in the cellular and circuit architectures of ventral pallidum contributes to the relapse to alcohol seeking. We show how this knowledge improves mechanistic understanding of current relapse prevention pharmacotherapies, how it may be used to tailor these against different forms of relapse and how it may help provide insights into the mental health problems frequently co‐morbid with alcohol‐use disorders.

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Opposing Regulation of Cocaine Seeking by Glutamate and GABA Neurons in the Ventral Pallidum

Cited by 72 publications

References 47 publications

Reward activity in ventral pallidum tracks satiety-sensitive preference and drives choice behavior

Reward activity in ventral pallidum tracks satiety-sensitive preference and drives choice behavior

Ventral pallidal GABAergic neurons control wakefulness associated with motivation through the ventral tegmental pathway

The ventral pallidum and relapse in alcohol seeking

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