Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass.

William Menegas,Kannan Umadevi Venkataraju,Sachie K Ogawa,Joseph F Bergan,Mitsuko Watabe-Uchida,Naoshige Uchida,Pavel Osten,Yoh Isogai

doi:10.7554/elife.10032

William Menegas, Kannan Umadevi Venkataraju + Show 6 more

Open Access

https://doi.org/10.7554/elife.10032

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Journal: eLife	Publication Date: Aug 31, 2015
Citations: 263	License type: CC BY 4.0

Affiliation: Harvard University, Cold Spring Harbor Laboratory

Abstract

Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense 'clusters' of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs.

Highlights

A longstanding challenge in neuroscience is to understand how neurons compute their output by integrating information from multiple sources
We found that populations of dopamine neurons projecting to most of these targets receive a similar set of inputs, while dopamine neurons projecting to TS (‘tail of the striatum’ or ‘posterior striatum’) are a clear outlier
We found that the distribution of labeled neurons in the ventral tegmental area (VTA)/substantia nigra pars compacta (SNc) was similar in cases with and without transsynaptic spread, indicating that transsynaptic spread between primarily infected dopamine neurons and other dopamine neurons did not lead to the nonspecific infection of all dopamine neurons (Figure 3—figure supplement 3)

Summary

Introduction

A longstanding challenge in neuroscience is to understand how neurons compute their output by integrating information from multiple sources. Midbrain dopamine neurons play important roles in various brain functions including motivation, reinforcement learning, and motor control (Wise, 2004; Redgrave and Gurney, 2006; Ikemoto, 2007; Schultz, 2007). Recording experiments have shown that many dopamine neurons signal reward prediction error (RPE): the discrepancy between predicted and actual reward value (Schultz et al, 1997; Bayer and Glimcher, 2005; Bromberg-Martin et al, 2010; Clark et al, 2012; Cohen et al, 2012; Schultz, 2015). It is thought that RPE coding is relatively uniform among dopamine neurons, and that dopamine’s major function is to guide behavior toward maximizing future rewards. Recent studies have suggested that there are at least two types of dopamine neurons, valuecoding and salience-coding (Matsumoto and Hikosaka, 2009), the extent of physiological diversity remains controversial (Fiorillo, 2013; Fiorillo et al, 2013a, 2013b)

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