title: Striosome-dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons.
abstract: The dopamine systems of the brain powerfully influence movement and motivation. We demonstrate that striatonigral fibers originating in striosomes form highly unusual bouquet-like arborizations that target bundles of ventrally extending dopamine-containing dendrites and clusters of their parent nigral cell bodies. Retrograde tracing showed that these clustered cell bodies in turn project to the striatum as part of the classic nigrostriatal pathway. Thus, these striosome-dendron formations, here termed "striosome-dendron bouquets," likely represent subsystems with the nigro-striato-nigral loop that are affected in human disorders including Parkinson's disease. Within the bouquets, expansion microscopy resolved many individual striosomal fibers tightly intertwined with the dopamine-containing dendrites and also with afferents labeled by glutamatergic, GABAergic, and cholinergic markers and markers for astrocytic cells and fibers and connexin 43 puncta. We suggest that the striosome-dendron bouquets form specialized integrative units within the dopamine-containing nigral system. Given evidence that striosomes receive input from cortical regions related to the control of mood and motivation and that they link functionally to reinforcement and decision-making, the striosome-dendron bouquets could be critical to dopamine-related function in health and disease.
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Jill R
authors.initials: JR
authors.lastname: Crittenden
authors.affiliation: Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139; Massachusetts Institute of Technology Media Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Tillberg
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Riad
authors.affiliation: Department of Biology, Brandeis University, Waltham, MA 02453; National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02453.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Shima
authors.affiliation: Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20814.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Gerfen
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Curry
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: David E
authors.initials: DE
authors.lastname: Housman
authors.affiliation: Department of Biology, Brandeis University, Waltham, MA 02453; National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02453.
authors.forename: Sacha B
authors.initials: SB
authors.lastname: Nelson
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA 02139; Massachusetts Institute of Technology Media Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Boyden
authors.affiliation: McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; graybiel@mit.edu.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Graybiel
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000502:physiology / Q000648:ultrastructure; D001931:Brain Mapping; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D050091:Dendrimers / Q000737:chemistry; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D051379:Mice; D017072:Neostriatum / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure*
chemical_list: D050091:Dendrimers; D004298:Dopamine
keywords: dopamine; expansion microscopy; striatum; striosome