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

PLoS One. 2015 Apr 1;10(4):e0123381. doi: 10.1371/journal.pone.0123381. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Mapping
  • Cholinergic Neurons / physiology*
  • Female
  • Interneurons / physiology*
  • Male
  • Mice, Inbred C57BL
  • Neostriatum / cytology
  • Neostriatum / physiology*
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Staining and Labeling

Substances

  • Receptors, Dopamine D1
  • Receptors, Dopamine D2

Grants and funding

2012CB837701 and 2012YQ03026005 from China Ministry of Science and Technology Science Fund for Creative Research Group of China (http://www.973.gov.cn/AreaAppl.aspx) to Minmin Luo. 91432114, 61178077, and 61421064 from National Natural Science Foundation of China (http://www.nsfc.gov.cn/) to Minmin Luo, Ling Fu, and Ling Fu, respectively. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.