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Cell. 2015 Jul 30;162(3):635-47. doi: 10.1016/j.cell.2015.07.014.

Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits.

Author information

1
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA.
2
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
3
Department of Biology, Stanford University, Stanford, CA 94305, USA.
4
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Nancy Pritzker Laboratory, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
5
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Neuroscience Program, Stanford University, Stanford, CA 94305, USA.
6
CNC Program, Stanford University, Stanford, CA 94305, USA.
7
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Nancy Pritzker Laboratory, Stanford University, Stanford, CA 94305, USA.
8
Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
9
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Electronic address: deissero@stanford.edu.

Abstract

Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

PMID:
26232229
PMCID:
PMC4790813
DOI:
10.1016/j.cell.2015.07.014
[Indexed for MEDLINE]
Free PMC Article

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