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

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.DOI: http://dx.doi.org/10.7554/eLife.10032.001

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

“…The dopamine-containing neurons of the SN receive inputs from multiple sources, as befits their pivotal position in modulating many forms of behavior (19)(20)(21). Striatonigral inputs are reported to exert direct inhibition over nigral dopamine-containing neurons (22).…”

Communication in Neural Circuits: Tools, Opportunities, and Challenges

“…Another form of IODE tracing has also recently been published (Menegas et al, 2015). Here, instead of using retrograde transport of a recombinase to specify starter cells, the authors used retrograde transport of TVA, packaged into an AAV (some AAVs can transduce CNS axons, though more variably and weakly than CAV or HSV).…”

“…Here, intact-brain analyses (as enabled by CLARITY and other whole-organ tissue transparency methods; Chung et al, 2013; Ertürk et al, 2012; Hama et al, 2011; Renier et al, 2014; Susaki et al, 2014; Richardson and Lichtman, 2015), especially when compatible with rich molecular information as may be obtained with multiplexed protein and RNA analysis, have provided key leverage, along with high-speed and high-resolution light-sheet microscopy methods such as COLM (CLARITY-optimized light-sheet microscopy; Tomer et al, 2014; Lerner et al, 2015; Tomer et al, 2015) and emerging methods for automated counting and quantitative analysis of circuit components (Kim et al, 2015b; Menegas et al, 2015). Integration of circuit-labeling techniques (Table S1) with analyses enabled by whole-brain transparency, labeling, imaging, and analysis methods (Table S2) promises to accelerate progress in dissecting IODEs, setting the stage for functional circuit investigation.…”

“…After IODE tracer injections (e.g., those involved in implementing TRIO; Schwarz et al, 2015), whole brains can be clarified (e.g., using CLARITY; adapted with permission from Chung et al, 2013) and intact IODEs can be visualized in the fully intact organ (Lerner et al, 2015, Menegas et al, 2015). Scale bars on optical coronal sections are 1 mm.…”

Clearing of fixed tissue: a review from a microscopist’s perspective

“…CLARITY, which uses as index-matching agent FocusClear (n ¼ 1.47), can provide crystal-clear entire mouse brains, 14 and indeed it has been successfully applied in combination with LSM. 15,39 Tissue processing with CLARITY requires at least 1 week (while it can be performed in 1 to 2 days with DBE). Recently, a speed-up of the clearing process has been achieved using stochastic electrotransport of lipids.…”