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

By Talia N. Lerner, Carrie Shilyansky, T. J. Davidson, Kathryn Evans, Kevin T. Beier, K. Zalocusky, A. Crow, R. Malenka, Liqun Luo, Raju Tomer and 1 more. 2015

715 citations recorded by the source corpus.

SUMMARY Recent controversy regarding 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, 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Molecular Biology

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Citations in the corpus

Coordinated and Compartmentalized Neuromodulation Shapes Sensory Processing in Drosophila (2015, positive): “…their anatomic and functional heterogeneity and the intricate wiring of their target neuropils (Beier et al., 2015; Fiorillo et al., 2013; Lammel et al., 2014; Lerner et al., 2015) have made it difficult to resolve how they can selectively alter synaptic signaling between different neural pathways.”
Circuit Architecture of VTA Dopamine Neurons Revealed by Systematic Input–Output Mapping (2015, neutral): “A similar input-output architecture also applies to SNc-DA circuitry (Lerner et al., 2015 [in this issue of Cell]).”
Wiring and Molecular Features of Prefrontal Ensembles Representing Distinct Experiences (2016, neutral): “The COLM system (described earlier in Tomer et al., 2014; Lerner et al., 2015) is optimized for high-resolution imaging and is most useful for studies requiring sub-cellular information, while the approach outlined here is optimized for speed and practicality in cellular resolution work, most…”
Dopamine neurons encoding long-term memory of object value for habitual behavior (2015, neutral): “Recent studies suggest that DA neurons are heterogeneous in terms of their functions (Brischoux et al., 2009; Lerner et al., 2015; Matsumoto and Hikosaka, 2009).”
Mapping of brain activity by automated volume analysis of immediate early genes (2016, neutral): “Those techniques are now starting to enable the streamlined analysis of axonal projections or cell positions in intact mouse brains in a manual or semi-automated way (Lerner et al., 2015; Menegas et al., 2015; Schwarz et al., 2015).”
Distinct dopamine receptor pathways underlie the temporal sensitivity of associative learning (2019, background): “Neural circuits involved in associative learning integrate sensory signals with rewarding or punishing reinforcement cues, frequently encoded by neuromodulatory dopaminergic neurons (DANs; Aso et al., 2014a; Bromberg-Martin et al., 2010; Lerner et al., 2015; Schultz et al., 1997; Waddell, 2016).”
Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors (2018, methodology): “In vivo imaging with fiber photometry Fiber photometry was performed as in (28, 63, 64).”
Schizophrenia, Dopamine and the Striatum: From Biology to Symptoms (2019, methodology): “Regions of the caudate receive inputs from nearly the entire cortex [11,17]; and, additionally, via various connections with the midbrain [13], the associative striatum acts as a moderator of communication between limbic and motor regions.”