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Dopamine neurons share common response function for reward prediction error

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Abstract

Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found marked homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we were able to describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal.

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Figure 1: Dopamine neurons share a common response function to unexpected rewards.
Figure 2: Prediction errors are calculated through scaled subtraction.
Figure 3: Scaled subtraction produces linear suppression across the population.
Figure 4: Expectation level determines proportional suppression of dopamine responses.
Figure 5: Cue response scales with reward response.
Figure 6: Dopamine neurons show high noise correlations in every task epoch.
Figure 7: Reward response correlates with response to aversive events.
Figure 8: Common response function allows even weakly responsive neurons to contribute.

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Acknowledgements

We thank J. Fitzgerald for assistance with analysis, J. Assad, R. Born, J. Maunsell, R. Wilson and members of the Uchida laboratory for discussions, C. Dulac for sharing resources, and K. Deisseroth (Stanford University) for the AAV-FLEX-ChR2 construct. This work was supported by a Sackler Fellowship in Psychobiology (N.E.) and US National Institutes of Health grants T32GM007753 (N.E.), F30MH100729 (N.E.), 2T32MH020017-16 (M.B.), 5T32MH020017-17 (M.B.), R01MH095953 (N.U.) and R01MH101207 (N.U.).

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N.E., J.T. and N.U. designed the experiments. N.E. and M.B. collected data for the variable-reward task. J.T. collected data for the variable-expectation task. N.E. analyzed data and wrote the manuscript, with comments from J.T. and N.U.

Corresponding author

Correspondence to Naoshige Uchida.

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The authors declare no competing financial interests.

Integrated supplementary information

Supplementary Figure 1 Recording sites.

(a, b) Schematic of recording locations for mice used in the variable-reward task (a, n = 5) and the variable-expectation task (b, n = 5). RN, red nucleus. SNc, substantia nigra pars compacta. SNr, substantia nigra pars reticulata.

Supplementary Figure 2 VTA neurons cluster into three response types.

(a) Responses of all neurons recorded in the variable-reward task (n = 170). Each row reflects the auROC values for a single neuron in the second before and after delivery of expected reward. Baseline is taken as one second before odor onset. Yellow, increase from baseline; cyan, decrease from baseline. Light-identified neurons are denoted by an * to the left of each row. (b) The first three principal components of the auROC curves. These values were used for unsupervised hierarchical clustering, as shown in the dendrogram on the right. (c) Average firing rates for the three clusters of neurons. Orange, unexpected reward trials. Black, expected reward trials. (d-f) Same conventions as a-c, except for neurons recorded in the variable-expectation task. All 31 light-identified dopamine neurons were classified as Type 1.

Supplementary Figure 3 Light identification of dopamine neurons.

(a) Raw signal from one example light-identified dopamine neuron in the variable-reward task. Blue bars, light pulses. (b) For the same neuron, mean waveforms for spontaneous (black) and light-evoked (blue) action potentials. (c) For the same neuron, raster plots for 20 Hz (left) and 50 Hz (right) laser stimulation. Each row is one trial of laser stimulation (10 pulses of laser). (d) Histogram of log P values for each neuron recorded in the variable-reward task (n = 170). The P values were derived from SALT (see Methods). Neurons with P < 0.001 and waveform correlations > 0.9 were considered identified (filled bars). (e, f) For light-identified neurons, probability of spiking (e) and latency to first spike (f) after laser pulses at different frequencies. Orange circles, mean across neurons. (g) Histogram of mean latencies (left) and latency standard deviations (right) in response to laser stimulation for all light-identified dopamine neurons in the variable-reward task. (h-n) Same conventions as a-g, but for neurons recorded in the variable-expectation task (n = 106).

Supplementary Figure 4 Putative and identified dopamine neurons respond similarly on the variable-reward task.

(a) Average putative dopamine neuron responses (mean ± s.e.m.) for different sizes of unexpected (orange circle) and expected (black circle) reward. Orange line, best-fit Hill function for unexpected reward. Black line, subtractive shift of the orange line. n = 84 neurons. (b) Response to unexpected 2.5 μL reward versus effect of expectation for this reward size. Line, best-fit linear regression. Grey dots, putative dopamine neurons. Blue dots, light-identified dopamine neurons. Pearson’s correlation across all neurons, P = 1 x 10−10. R, correlation coefficient. (c) Baseline firing rates versus effect of expectation (averaged across reward sizes). P = 0.01. (d) Difference between reward-predicting odor and nothing-predicting odor versus difference between unexpected reward and expected reward. P = 3 x 10−6.

Supplementary Figure 5 Subtraction is scaled for each reward size.

(a-f) For identified dopamine neurons in the variable-reward experiment (n = 40), response to unexpected reward versus effect of expectation for 0.1 μL (a, P = 1.1 x 10−10), 0.3 μL (b, P = 4.4 x 10−9), 1.2 μL (c, P = 3.4 x 10−9), 5 μL (d, P = 1.9 x 10−8), 10 μL (e, P = 5 x 10−5), and 20 μL (f, P = 8.1 x 10−5) reward. R, correlation coefficient.

Supplementary Figure 6 Noise correlations for pairs of putative dopamine and GABA neurons.

(a, b) Noise correlations (mean ± s.e.m.) between pairs of simultaneously-recorded putative dopamine (Type 1) and GABA (Type 2) neurons in the variable-reward experiment (a, n = 59 pairs) and the variable-expectation experiment (b, n = 44 pairs). Correlations were calculated by examining trial-by-trial variations in spiking during different task epochs (see Methods). Grey bars, correlations on simultaneous trials. Black bars, correlations in which one neuron’s data was shifted by one trial. (c, d) Histograms of noise correlations between pairs of simultaneously-recorded putative dopamine and GABA neurons. Data are combined from both the variable-reward and variable-expectation experiments, and reflect correlations during the reward-predicting cue (c) and during delivery of expected reward (d). Filled bars, significant noise correlation (P < 0.05, Pearson’s correlation). Empty bars, n.s. Dotted lines, mean noise correlation.

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Eshel, N., Tian, J., Bukwich, M. et al. Dopamine neurons share common response function for reward prediction error. Nat Neurosci 19, 479–486 (2016). https://doi.org/10.1038/nn.4239

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