In the scope of the research project 175/20 - The role of nucleus accumbens in the perception of natural rewards, led by Carina Cunha and supported by the BIAL Foundation, it was published the paper Involvement of nucleus accumbens D2–medium spiny neurons projecting to the ventral pallidum in anxiety-like behaviour in the Journal of Psychiatry & Neuroscience. In this study, the contribution of a specific population of dopaminergic neurons in a central nucleus for emotional behaviors is highlighted, now in the context of anxiety.
ABSTRACT
Background: The nucleus accumbens (NAcc) is a crucial brain region for emotionally relevant behaviours. The NAcc is mainly composed of medium spiny neurons (MSNs) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). The D1-MSNs project to the ventral tegmental area (VTA) and the ventral pallidum (VP), whereas the D2-MSNs project only to the VP. The D1- and D2-MSNs have been associated with depression-like behaviours, but their contribution to anxiety remains to be determined.
Methods: We used optogenetic tools to selectively manipulate D1-MSN projections from the NAcc core to the VP or VTA and D2-MSN projections to the VP during validated anxiety-producing behavioural procedures in naive mice. In addition, we assessed the effects of optical stimulation on neuronal activity using in vivo electrophysiologic recordings in anesthetized animals.
Results: Optogenetic activation of D1-MSN projections to the VTA or VP did not trigger anxiety-like behaviour. However, optical activation of D2-MSN projections to the VP significantly increased anxiety-like behaviour. This phenotype was associated with a decrease in the neuronal activity of putative GABAergic neurons in the VP. Importantly, pretreating D2-MSN–VP animals with the γ-aminobutyric acid modulator diazepam prevented the optically triggered anxiety-like behaviour.
Limitations: The exclusive use of males in the behavioural tests limits broader interpretation of the findings. Although we used optogenetic conditions that trigger quasi-physiologic changes, there are caveats associated with the artificial manipulation of neuronal activity.
Conclusion: The D2-MSN–VP projections contributed to the development of anxiety-like behaviour, through modulation of GABAergic activity in the VP.
