Distributed and Mixed Information in Monosynaptic Inputs to Dopamine Neurons.
Dopamine neurons encode the difference between actual and predicted reward, or reward prediction error (RPE). Although many models have been proposed to account for this computation, it has been difficult to test these models experimentally. Here we established an awake electrophysiological recording system, combined with rabies virus and optogenetic cell-type identification, to characterize the firing patterns of monosynaptic inputs to dopamine neurons while mice performed classical conditioning tasks. We found that each variable required to compute RPE, including actual and predicted reward, was distributed in input neurons in multiple brain areas. Further, many input neurons across brain areas signaled combinations of these variables. These results demonstrate that even simple arithmetic computations such as RPE are not localized in specific brain areas but, rather, distributed across multiple nodes in a brain-wide network. Our systematic method to examine both activity and connectivity revealed unexpected redundancy for a simple computation in the brain.
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Ju
J
Tian
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Ryan
R
Huang
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; The Solomon H. Snyder Department of Neuroscience, Brain Science Institute, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
Jeremiah Y
JY
Cohen
Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya 464-8601, Japan.
Fumitaka
F
Osakada
Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal.
Dmitry
D
Kobak
Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon 1400-038, Portugal.
Christian K
CK
Machens
Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Edward M
EM
Callaway
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: uchida@mcb.harvard.edu.
Naoshige
N
Uchida
Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: mitsuko@mcb.harvard.edu.
Mitsuko
M
Watabe-Uchida
D000818:Animals; D001931:Brain Mapping / Q000523:psychology; D003214:Conditioning, Classical / Q000502:physiology*; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D059290:Dopaminergic Neurons / Q000502:physiology*; D008297:Male; D051379:Mice; D009434:Neural Pathways / Q000502:physiology*; D012201:Reward; D013569:Synapses / Q000502:physiology*