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

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
Keywords: neurotropic, brain, dopamine, neurons
Subjects: Medicine and health
Depositing User: Anne Manyande
Date Deposited: 13 Sep 2023 08:28
Last Modified: 06 Feb 2024 16:16
URI: https://repository.uwl.ac.uk/id/eprint/10368

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