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bioRxiv · 10.1101/2022.05.23.493058

Involvement of nucleus accumbens D2-MSN projections to the ventral pallidum in anxious-like behavior

Correia, R.·Domingues, A. V.·Coimbra, B.·Vieitas-Gaspar, N.·Sousa, N.·Pinto, L.·Rodrigues, A. J.·Soares-Cunha, C.
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Abstract

The nucleus accumbens (NAc) is a crucial brain region for emotionally-relevant behaviors. The NAc is mainly composed of medium spiny neurons (MSN) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). D1-MSNs project to the ventral tegmental area (VTA) and ventral pallidum (VP), while D2-MSNs project only to the VP. In this work, we selectively manipulated D1-MSN projections to the VP and VTA, and D2-MSN projections to the VP during classical anxiety behavioral paradigms in naive mice. We found that optogenetic activation of D1-MSN to VP or VTA did not trigger significant anxious-like behaviors. Interestingly, optical activation of D2-MSN-VP projections significantly increased anxious-like behavior in all of the tests performed. This phenotype was associated with a decrease in the activity of VP putative GABAergic neurons. Importantly, pre-treating D2-MSN-VP animals with the GABA modulator diazepam prevented the optically-triggered anxious-like behavior. Overall, our results suggest that D2-MSN-VP projections contribute for the development of anxious-like behavior, through modulation of GABAergic activity in the VP.

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Correia, R., Domingues, A. V., Coimbra, B., Vieitas-Gaspar, N., Sousa, N., Pinto, L., Rodrigues, A. J., Soares-Cunha, C.. 2022-05-23. Involvement of nucleus accumbens D2-MSN projections to the ventral pallidum in anxious-like behavior. https://doi.org/10.1101/2022.05.23.493058

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