The Lateral Preoptic Area and Its Projection to the VTA Regulate VTA Activity and Drive Complex Reward Behaviors

Adam Gordon-Fennell,Stève Desaivre,Michela Marinelli,Lydia Gordon-Fennell

doi:10.3389/fnsys.2020.581830

Adam Gordon-Fennell, Stève Desaivre + Show 2 more

Open Access

https://doi.org/10.3389/fnsys.2020.581830

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Abstract

The ventral tegmental area (VTA) underlies motivation and reinforcement of natural rewards. The lateral preoptic area (LPO) is an anterior hypothalamic brain region that sends direct projections to the VTA and to other brain structures known to regulate VTA activity. Here, we investigated the functional connection between the LPO and subpopulations of VTA neurons and explored the reinforcing and valence qualities of the LPO in rats. We found that the LPO and the LPO→VTA pathway inhibit the activity of VTA GABA neurons and have mixed effects on VTA dopamine neurons. Furthermore, we found that the LPO supports operant responding but drives avoidance, and we explored the apparent discrepancy between these two results. Finally, using fiber photometry, we show that the LPO signals aversive events but not rewarding events. Together, our findings demonstrate that the LPO modulates the activity of the VTA and drives motivated behavior and represents an overlooked modulator of reinforcement.

Highlights

The lateral preoptic area (LPO) is an understudied region of the hypothalamus that is deeply interconnected with the brain reward system
These results indicate that the LPO sends direct GABAergic and glutamatergic projections to the ventral tegmental area (VTA) and that GABA makes up a larger proportion of this projection in rostral portions of the LPO
We found that the stimulation of the LPO produces primarily inhibition on VTAGABA neurons and mixed effects on VTADopamine neurons

Summary

Introduction

The lateral preoptic area (LPO) is an understudied region of the hypothalamus that is deeply interconnected with the brain reward system. Previous work from our lab showed that stimulation of the LPO decreases VTAGABA firing and increases VTADopamine firing; it produces reinstatement of reward-seeking (Gordon-Fennell et al, 2020), which supports the hypothesis that the LPO can drive behavior through disinhibition of dopamine neurons (Subramanian et al, 2018) From these data, LPO Drive Complex Reward Behaviors it is unclear if the LPO modulates the VTA through direct or indirect projections to the VTA (Matsuda et al, 2009; Russo and Nestler, 2013; Aransay et al, 2015; Barker et al, 2016). The capacity of the LPO and LPO→VTA pathway to regulate these behaviors remains unclear

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