Publication Date:
2015-09-01
Description:
Dopamine neurons are thought to facilitate learning by comparing actual and expected reward. Despite two decades of investigation, little is known about how this comparison is made. To determine how dopamine neurons calculate prediction error, we combined optogenetic manipulations with extracellular recordings in the ventral tegmental area while mice engaged in classical conditioning. Here we demonstrate, by manipulating the temporal expectation of reward, that dopamine neurons perform subtraction, a computation that is ideal for reinforcement learning but rarely observed in the brain. Furthermore, selectively exciting and inhibiting neighbouring GABA (gamma-aminobutyric acid) neurons in the ventral tegmental area reveals that these neurons are a source of subtraction: they inhibit dopamine neurons when reward is expected, causally contributing to prediction-error calculations. Finally, bilaterally stimulating ventral tegmental area GABA neurons dramatically reduces anticipatory licking to conditioned odours, consistent with an important role for these neurons in reinforcement learning. Together, our results uncover the arithmetic and local circuitry underlying dopamine prediction errors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567485/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4567485/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eshel, Neir -- Bukwich, Michael -- Rao, Vinod -- Hemmelder, Vivian -- Tian, Ju -- Uchida, Naoshige -- F30 MH100729/MH/NIMH NIH HHS/ -- F30MH100729/MH/NIMH NIH HHS/ -- R01 MH095953/MH/NIMH NIH HHS/ -- R01 MH101207/MH/NIMH NIH HHS/ -- R01MH095953/MH/NIMH NIH HHS/ -- R01MH101207/MH/NIMH NIH HHS/ -- T32 GM007753/GM/NIGMS NIH HHS/ -- T32GM007753/GM/NIGMS NIH HHS/ -- England -- Nature. 2015 Sep 10;525(7568):243-6. doi: 10.1038/nature14855. Epub 2015 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26322583" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Conditioning, Classical
;
Dopamine/*metabolism
;
Dopaminergic Neurons/*metabolism
;
GABAergic Neurons/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
;
*Models, Neurological
;
Neural Pathways/*physiology
;
Odors/analysis
;
Optogenetics
;
Reinforcement (Psychology)
;
Reward
;
Time Factors
;
Ventral Tegmental Area/*cytology/*physiology
;
gamma-Aminobutyric Acid/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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