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

Talia N. Lerner, Carrie Shilyansky, Thomas J. Davidson, Kathryn E. Evans, Kevin T. Beier, Kelly A. Zalocusky, Ailey K. Crow, Robert C. Malenka, Liqun Luo, Raju Tomer, Karl Deisseroth*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

462 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)635-647
Number of pages13
Issue number3
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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