Whole-brain mapping of inputs to projection neurons and cholinergic interneurons in the dorsal striatum.

Qingchun Guo,Qiru Feng,Fuqiang Xu,Xiaobin He,Rui Lin,Daqing Wang,Minmin Luo,Ling Fu,Benjamin Arenkiel

doi:10.1371/journal.pone.0123381

Abstract

The dorsal striatum integrates inputs from multiple brain areas to coordinate voluntary movements, associative plasticity, and reinforcement learning. Its projection neurons consist of the GABAergic medium spiny neurons (MSNs) that express dopamine receptor type 1 (D1) or dopamine receptor type 2 (D2). Cholinergic interneurons account for a small portion of striatal neuron populations, but they play important roles in striatal functions by synapsing onto the MSNs and other local interneurons. By combining the modified rabies virus with specific Cre- mouse lines, a recent study mapped the monosynaptic input patterns to MSNs. Because only a small number of extrastriatal neurons were labeled in the prior study, it is important to reexamine the input patterns of MSNs with higher labeling efficiency. Additionally, the whole-brain innervation pattern of cholinergic interneurons remains unknown. Using the rabies virus-based transsynaptic tracing method in this study, we comprehensively charted the brain areas that provide direct inputs to D1-MSNs, D2-MSNs, and cholinergic interneurons in the dorsal striatum. We found that both types of projection neurons and the cholinergic interneurons receive extensive inputs from discrete brain areas in the cortex, thalamus, amygdala, and other subcortical areas, several of which were not reported in the previous study. The MSNs and cholinergic interneurons share largely common inputs from areas outside the striatum. However, innervations within the dorsal striatum represent a significantly larger proportion of total inputs for cholinergic interneurons than for the MSNs. The comprehensive maps of direct inputs to striatal MSNs and cholinergic interneurons shall assist future functional dissection of the striatal circuits.

Highlights

As the key input station in the basal ganglia, the dorsal striatum coordinates neuronal signals from multiple cortical and subcortical regions and plays a critical role in voluntary movements, motor learning, cognition, and emotion [1,2,3,4]
We first confirmed the accuracy of using dopamine receptor type 1 (D1)-Cre, dopamine receptor type 2 (D2)-Cre, and choline acetyltransferase (ChAT)-Cre mouse lines to genetically target striatal D1 medium spiny neurons (MSNs), D2 MSNs, and cholinergic interneurons, respectively
Following stereotaxic infusion of the Cre-dependent associated virus (AAV)-DIO-enhanced membrane GFP (EmGFP) vectors into the D1-Cre mice (Fig 1A), we observed dense EmGFP labeling in the dorsal striatum as well as the entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNr), the major targets of D1 MSNs in the direct pathway [5,6] (Fig 1B)

Summary

Introduction

As the key input station in the basal ganglia, the dorsal striatum coordinates neuronal signals from multiple cortical and subcortical regions and plays a critical role in voluntary movements, motor learning, cognition, and emotion [1,2,3,4]. D1 MSNs project to the internal globus pallidus (GPi)/entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNr), which forms the direct pathway [5,6]. D2-type MSNs indirectly activate the GPi-SNr complex through the external globus pallidus (GPe) and the excitatory subthalamic nucleus, thereby forming the indirect pathway. Dysfunction of the basal ganglia system is associated with multiple neurological disorders, such as Parkinson's disease and Huntington's disease [9,10]

Methods

Results

Conclusion