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

eLife digest

Most neurons send their messages to recipient neurons by releasing a substance called a ‘neurotransmitter’ that binds to receptors on the target cell. The sites of this type of signal transmission are called synapses. Some small populations of neurons modulate the activity of hundreds or thousands of these synapses all across the brain by releasing ‘neuromodulators’ that affect how they work. These neuromodulators are essential because they broadcast information that is likely to be useful to many brain regions, like a ‘news channel’ for the brain.

One important neuromodulator in the mammalian brain is dopamine, which contributes to motivation, learning, and the control of movement. Clusters of cells deep in the brain release dopamine, and people with Parkinson's disease gradually lose these cells. This makes it increasingly difficult for their brains to produce the correct amount of dopamine, and results in symptoms such as tremors and stiff muscles.

Individual dopamine neurons typically send information to a single part of the brain. This suggests that dopamine neurons with different targets might have different roles. To explore this possibility, Menegas et al. classified dopamine neurons in the mouse brain into eight types based on the areas to which they project, and then mapped which neurons send input signals to each type. These inputs are likely to shape the activity of each type (that is, their ‘message’ to the rest of the brain). The mapping revealed that most dopamine neurons do not receive substantial input from the area to which they project (i.e., they do not form ‘closed loops’). Instead, most of their input comes from a common set of brain regions, including a particularly large number of inputs from the ventral striatum.

However, Menegas et al. found one exception. Dopamine neurons that target part of the brain called the posterior striatum receive relatively little input from the ventral striatum. Their input comes instead from a set of other brain structures, and in particular from a region called the subthalamic nucleus. Electrical stimulation of the subthalamic nucleus can help to relieve the symptoms of Parkinson's disease. Therefore, the results presented by Menegas et al. suggest that this population of dopamine neurons might be particularly relevant to Parkinson's disease and that focusing future studies on them could ultimately be beneficial for patients.

DOI: http://dx.doi.org/10.7554/eLife.10032.002