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Projections from D2 Neurons in Different Subregions of Nucleus Accumbens Shell to Ventral Pallidum Play Distinct Roles in Reward and Aversion

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Abstract

The nucleus accumbens shell (NAcSh) plays an important role in reward and aversion. Traditionally, NAc dopamine receptor 2-expressing (D2) neurons are assumed to function in aversion. However, this has been challenged by recent reports which attribute positive motivational roles to D2 neurons. Using optogenetics and multiple behavioral tasks, we found that activation of D2 neurons in the dorsomedial NAcSh drives preference and increases the motivation for rewards, whereas activation of ventral NAcSh D2 neurons induces aversion. Stimulation of D2 neurons in the ventromedial NAcSh increases movement speed and stimulation of D2 neurons in the ventrolateral NAcSh decreases movement speed. Combining retrograde tracing and in situ hybridization, we demonstrated that glutamatergic and GABAergic neurons in the ventral pallidum receive inputs differentially from the dorsomedial and ventral NAcSh. All together, these findings shed light on the controversy regarding the function of NAcSh D2 neurons, and provide new insights into understanding the heterogeneity of the NAcSh.

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Acknowledgements

We thank Dr. Yi Rao for generously providing the D2-Cre mice. We thank Dr. MM Luo and Dr. KX Yuan for help with the virus. We also thank Dr. Wei Shen for generously providing the VGAT-ires-Cre and VGLUT2-ires-Cre mice. We thank Dr. FQ Xu in providing the Rabies virus (BrainVTA). This research was supported by National Science Foundation of China grants 31571095 and 91332122, a Key Scientific Technological Innovation Research project from the Ministry of Education, a grant from Insitute Guo Qiang at Tsinghua University and funding from the Beijing Program on the Study of Functional Chips and Related Core Technologies of Brain-inspired Computing Systems.

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  1. Yun Yao and Ge Gao have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Brain and Intelligence, Department of Biomedical Engineering, and McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China

    Yun Yao, Ge Gao, Kai Liu, Xin Shi & Sen Song

  2. Center for Brain-Inspired Computing Research, Beijing Innovation Center for Future Chips, Tsinghua University, Beijing, 100084, China

    Yun Yao & Sen Song

  3. School of Life Science, Tsinghua University, Beijing, 100084, China

    Ge Gao, Kai Liu & Mingxiu Cheng

  4. National Institute of Biological Sciences, Beijing, 102206, China

    Mingxiu Cheng

  5. Department of Psychology, University of Michigan, Ann Arbor, MI, 48109, USA

    Yan Xiong

  6. Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China

    Yun Yao

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  1. Yun Yao
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Yao, Y., Gao, G., Liu, K. et al. Projections from D2 Neurons in Different Subregions of Nucleus Accumbens Shell to Ventral Pallidum Play Distinct Roles in Reward and Aversion. Neurosci. Bull. 37, 623–640 (2021). https://doi.org/10.1007/s12264-021-00632-9

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