The Systems Biology of Parkinson’s disease (PD) will be underpinned by new measurement techniques. This is particularly true of the pathology of PD, where recent developments in brain imaging have offered new insights into the morphology of dopaminergic (DA) neurons that have profound implications for the special vulnerability and role of this class of neurons. In this chapter, we describe these new morphological measurement techniques and how they contribute to our understanding of PD.
We begin with an overview of the conventional understanding of the morphology of DA neurons, as seen from a historical perspective. We then describe novel imaging techniques that reveal important new structural information concerning DA neurons. In particular, we outline some new methods for labeling DA neurons, together with the technical aspects of labeling and measuring axonal structure.
Detail morphological images of DA neurons derived from this new approach are used to elucidate the role of DA neurons in PD. First, we point out how the new images reveal how DA neurons have a massive axonal arborization in the striatum. This arborization is on a scale not previously known, and of a form that implies both a particular vulnerability and a redundancy in DA neurons. Second, we describe how the imaging results indicate that DA neurons innervate both the striosome and the matrix compartments of the striatum. This dual innervation has implications for reinforcement learning in the basal ganglia and for how normal behavior is driven and how it may be disrupted by Levodopa PD therapies.
The chapter concludes with a summary of how these results contribute to our understanding of PD and how it forms a part of the Systems Biology of PD.
Substantia Nigra Ventral Tegmental Area Infected Neuron Axon Fiber Axonal Arborization
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Competing Interest Statements
The authors declare that they have no competing financial interests.
Acknowledgments This study was supported by Grants-in-Aid for Scientific Research 22500307, 22500308, 22592041, and General Insurance Association of Japan, ZENKYOREN, Mitsui Sumitomo Insurance Welfare Foundation, and Shiga Prefecture Rehabilitation Centre.
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