• Investigations of brain-wide functional and structural networks of dopaminergic and CamKII?-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies

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Document Title

Investigations of brain-wide functional and structural networks of dopaminergic and CamKII?-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies

Author

Zheng N. Gui Z. Liu X. Wu Y. Wang H. Cai A. Wu J. Li X. Kaewborisuth C. Zhang Z. Wang Q. Manyande A. Xu F. Wang J.

Affiliations

Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics National Center for Magnetic Resonance in Wuhan Wuhan Institute of Physics and Mathematics Innovation Academy for Precision Measurement Science and Technology Chinese Academy of Sciences-Wuhan National Laboratory for Optoelectronics Wuhan 430071 China; University of Chinese Academy of Sciences Beijing 100049 China; Department of Anaesthesia and Intensive Care Peter Hung Pain Research Institute The Chinese University of Hong Kong SAR Hong Kong; Shenzhen Key Laboratory of Viral Vectors for Biomedicine Key Laboratory of Quality Control Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products Administration NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products The Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions Shenzhen 518055 China; College of Integrative Medicine Fujian University of Traditional Chinese Medicine Fujian Fuzhou China; Virology and Cell Technology Research Team National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency (NSTDA) Pathumthani 12120 Thailand; Department of Neuroscience and Mahoney Institute for Neurosciences Perelman School for Medicine University of Pennsylvania Philadelphia PA 19104 United States; School of Human and Social Sciences University of West London Middlesex TW8 9GA United Kingdom; Institute of Neuroscience and Brain Diseases Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science Hubei Xiangyang China

Type

Article

Source Title

Journal of Translational Medicine

ISSN

14795876

Year

2023

Volume

21

Issue

1

Open Access

All Open Access Gold Green

Publisher

BioMed Central Ltd

DOI

10.1186/s12967-023-04362-6

Abstract

Background: The ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition while CamKII?-positive neurons composed mainly of glutamatergic and some dopaminergic neurons participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated. Methods: In this study we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKII?-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore the cre-dependent antegrade transsynaptic viral tracer H129?TK-TT was applied to label the outputs of VTA neurons. Results: We found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC Cg and Septum. More regions responded to selective activation of VTA CamKII?-positive neurons resulting in increased BOLD signals in VTA Insula mPFC MC_R (Right) Cg Septum Hipp TH_R PtA_R and ViC_R. Along with DREADD-BOLD analysis further neuronal tracing identified multiple cortical (MC mPFC) and subcortical (Hipp TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKII?-positive neurons. Conclusions: Our study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions. ? 2023 BioMed Central Ltd. part of Springer Nature.

Industrial Classification

N/A

Knowledge Taxonomy Level 1

Biological Sciences

Knowledge Taxonomy Level 2

Neuroscience and behavior

Knowledge Taxonomy Level 3

Cellular and molecular neuroscience

License

CC BY

Rights

Authors

Publication Source

WOS

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