No âmbito do projeto de investigação 175/20 - The role of nucleus accumbens in the perception of natural rewards, liderado por Carina Cunha e apoiado pela Fundação BIAL, foi publicado o artigo Involvement of nucleus accumbens D2–medium spiny neurons projecting to the ventral pallidum in anxiety-like behaviour na revista científica Journal of Psychiatry & Neuroscience. Neste estudo, evidencia-se o contributo de uma população específica de neurónios dopaminérgicos num núcleo central para comportamentos emocionais, agora no contexto de ansiedade.
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.
