Whole-Brain Reconstruction of Neurons in the Ventral Pallidum Reveals Diverse Projection Patterns.

Qiru Feng,Rui Lin,Hui Gong,Minmin Luo,Ruiyu Wang,Sile An,Anan Li

doi:10.3389/fnana.2021.801354

Abstract

The ventral pallidum (VP) integrates reward signals to regulate cognitive, emotional, and motor processes associated with motivational salience. Previous studies have revealed that the VP projects axons to many cortical and subcortical structures. However, descriptions of the neuronal morphologies and projection patterns of the VP neurons at the single neuron level are lacking, thus hindering the understanding of the wiring diagram of the VP. In this study, we used recently developed progress in robust sparse labeling and fluorescence micro-optical sectioning tomography imaging system (fMOST) to label mediodorsal thalamus-projecting neurons in the VP and obtain high-resolution whole-brain imaging data. Based on these data, we reconstructed VP neurons and classified them into three types according to their fiber projection patterns. We systematically compared the axonal density in various downstream centers and analyzed the soma distribution and dendritic morphologies of the various subtypes at the single neuron level. Our study thus provides a detailed characterization of the morphological features of VP neurons, laying a foundation for exploring the neural circuit organization underlying the important behavioral functions of VP.

Highlights

The ventral pallidum (VP), a major structure of the basal ganglia, represents a central station in the brain reward circuits (Heimer et al, 1982; Zahm, 1989)
The VP is considered a key node in the brain reward system, but all existing mesoscale connectivity of the VP neurons only shows the overall projections of a large number of neurons (Zahm, 1989; Bell et al, 1995; Mahler et al, 2014; Root et al, 2015)
Our results reveal that VP neurons can be classified into at least three major subtypes with distinct axonal projection patterns and dendritic morphologies, suggesting functional heterogeneity among individual VP neurons

Summary

Introduction

The ventral pallidum (VP), a major structure of the basal ganglia, represents a central station in the brain reward circuits (Heimer et al, 1982; Zahm, 1989). With the development of sparse labeling methods (Rotolo et al, 2008; Lin et al, 2018) and brain-wide precision imaging (Economo et al, 2016; Gong et al, 2016), more research attention has been focused on the whole-brain reconstruction of individual neurons (Peng et al, 2015; Economo et al, 2016; Li et al, 2018; Winnubst et al, 2019), including cortical neurons (Economo et al, 2016; Guo et al, 2017); cholinergic neurons (Li et al, 2018); dopamine neurons (Lin et al, 2018); serotonin neurons (Ren et al, 2019); and striatal, thalamic, cortical, and claustral neurons (Han, 2020) These results demonstrate that a neuron population within a brain area often exhibits multiple patterns of axonal projection at the single-cell level, which suggests a more precise circuit organization underlying the functional roles of a given neuron population

Methods

Results

Conclusion