Zheng, N, Gui, Z, Liu, X, Wu, Y, Wang, H, Cai, A, Wu, J, Li, X, Kaewborisuth, C, Zhang, Z, Wang, Q, Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722, Xu, F and Wang, J (2023) Investigations of brain-wide functional and structural networks of dopaminergic and CamKIIα-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies. Journal of Translational Medicine, 21 (543). ISSN 1479-5876

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Abstract

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 CamKIIα-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 CamKIIα-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 H129ΔTK-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 CamKIIα-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 CamKIIα-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.

Keywords: DREADD; HSV; Neural networks; Ventral tegmental area (VTA); fMRI.

Item Type:	Article
Identifier:	10.1186/s12967-023-04362-6
Keywords:	neurotropic, brain, dopamine, neurons
Subjects:	Medicine and health
Depositing User:	Anne Manyande
Date Deposited:	13 Sep 2023 08:28
Last Modified:	18 Mar 2024 11:13
URI:	https://repository.uwl.ac.uk/id/eprint/10368

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