A Whole-Brain Connectivity Map of VTA and SNc Glutamatergic and GABAergic Neurons in Mice.

Sile An,Qingming Luo,Zhao Feng,Xin Liu,Anan Li,Yue Luo,Hui Gong,Lei Deng,Xiangning Li,Zhangheng Ding,Yutong Han,Peilin Zhao

doi:10.3389/fnana.2021.818242

Abstract

The glutamatergic and GABAergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) mediated diverse brain functions. However, their whole-brain neural connectivity has not been comprehensively mapped. Here we used the virus tracers to characterize the whole-brain inputs and outputs of glutamatergic and GABAergic neurons in VTA and SNc. We found that these neurons received similar inputs from upstream brain regions, but some quantitative differences were also observed. Neocortex and dorsal striatum provided a greater share of input to VTA glutamatergic neurons. Periaqueductal gray and lateral hypothalamic area preferentially innervated VTA GABAergic neurons. Specifically, superior colliculus provided the largest input to SNc glutamatergic neurons. Compared to input patterns, the output patterns of glutamatergic and GABAergic neurons in the VTA and SNc showed significant preference to different brain regions. Our results laid the anatomical foundation for understanding the functions of cell-type-specific neurons in VTA and SNc.

Highlights

The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as nuclei associated with dopamine release, are involved in reward processing, reinforcement learning, and motor control (Wise, 2004; Fields et al, 2007; Ikemoto, 2007; Cohen et al, 2012)
To map the whole-brain monosynaptic inputs to glutamatergic and GABAergic neurons in VTA and SNc, we used RV-mediated transsynaptic retrograde tracing, which used the modified rabies virus EnvA-DG-green fluorescent protein (GFP) combined with a Cre/LoxP gene-expression strategy (Wickersham et al, 2007; Miyamichi et al, 2011; Watabe-Uchida et al, 2012; Wall et al, 2013)
The location of the vast majority of starter cells was restricted to the VTA and SNc (Supplementary Figures 1A,C), we found a small number of coexpression of adenoassociated virus (AAV)-BFP and RV-GFP neurons in neighboring nuclei: the midbrain reticular nucleus (MRN), substantia nigra, reticular part (SNr), midbrain reticular nucleus, retrorubral area (RR)

Summary

Introduction

The ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as nuclei associated with dopamine release, are involved in reward processing, reinforcement learning, and motor control (Wise, 2004; Fields et al, 2007; Ikemoto, 2007; Cohen et al, 2012) Dysfunction in these two brain regions can lead to some neurological disorders such as drug addiction, depression and Parkinson’s disease (Wise, 2004; Nestler and Carlezon, 2006; Deisseroth, 2014; Lammel et al, 2014; Volkow and Morales, 2015; Luscher, 2016; Schultz, 2016). These two types of neurons in the VTA and SNc play pivotal roles in multiple brain functions such as sleep and wakefulness (Yu et al, 2019), innate defensive behaviors

Methods

Results

Conclusion