Serotonergic neurons signal reward and punishment on multiple timescales

  1. Jeremiah Y Cohen  Is a corresponding author
  2. Mackenzie W Amoroso
  3. Naoshige Uchida
  1. Harvard University, United States
  2. The Johns Hopkins University School of Medicine, United States
8 figures

Figures

Figure 1 with 2 supplements
Behavioral task.

(A) Structure of individual trials. (B) Average lick rate for all animals during each trial type. (C) Representative sequence of trials from one experiment. Each point represents an odor cue. Shaded …

https://doi.org/10.7554/eLife.06346.003
Figure 1—figure supplement 1
Histogram of lick rate during tones indicating block transitions, for experiments in which reward blocks alternated with punishment blocks.
https://doi.org/10.7554/eLife.06346.004
Figure 1—figure supplement 2
Mice treat air puffs as punishments.

(A) Mice performed a two-alternative forced choice task, in which they chose between a water reward and a water reward together with an air puff, indicating their response by moving to the …

https://doi.org/10.7554/eLife.06346.005
Identifying serotonergic neurons.

(A) Example voltage trace from 10 pulses of 10-Hz light stimulation (cyan bars; light duration, 5 ms). Each light-triggered spike is shown below. The lower right is the first two principal …

https://doi.org/10.7554/eLife.06346.006
Figure 3 with 4 supplements
A population of serotonergic neurons is more or less active during blocks of reward trials than punishment trials.

(A) Average firing rates of four example serotonergic neurons during reward trials (black) and punishment trials (orange). Shaded regions denote S.E.M. Note the higher pre-trial firing rate during …

https://doi.org/10.7554/eLife.06346.007
Figure 3—figure supplement 1
Raster plots showing spike times during 40 trials for the four example neurons in Figure 3A.
https://doi.org/10.7554/eLife.06346.008
Figure 3—figure supplement 2
(A) Normalized mean ± S.E.M. firing rate within reward and punishment blocks for the positive-coding serotonergic neurons.

Note the build-up and build-down activity within blocks. (B) Raw firing rates for reward and punishment blocks for six example serotonergic neurons with tonic firing rate differences across blocks. …

https://doi.org/10.7554/eLife.06346.009
Figure 3—figure supplement 3
(A) Trial-by-trial scatter plot of lick rate against spike rate for an example serotonergic neuron.

(B) Pearson correlation coefficient of trial-by-trial lick rate and spike rate across serotonergic neurons. The two neurons with significant correlations are indicated in gray. (C) Firing rate …

https://doi.org/10.7554/eLife.06346.010
Figure 3—figure supplement 4
Example activity of a dopaminergic neuron with a smaller response to predicted reward than unpredicted reward-predicting cue.
https://doi.org/10.7554/eLife.06346.011
Figure 4 with 1 supplement
Serotonergic neurons are briefly excited or inhibited by punishments or reward-predicting cues.

(A) Average firing rates of two example serotonergic neurons during punishment trials. CS and US analysis windows are shaded in gray. (B) Area under the ROC curve for punishment trials for all …

https://doi.org/10.7554/eLife.06346.012
Figure 4—figure supplement 1
(A) Area under the ROC curve for reward (water) vs punishment (air puff) trials for serotonergic neurons, sorted by the sum of the auROC.

Yellow indicates excitation, blue indicates inhibition, and black indicates no change relative to baseline. (B) Histogram of changes in firing rate during the CS and US epochs of reward vs …

https://doi.org/10.7554/eLife.06346.013
Correlations between serotonergic neuron response features.

(A) Difference in firing rate during the 2-s pre-trial epoch vs the difference in firing rate during the CS (reward − punishment), corrected for baseline differences. (B) Area under the ROC curve …

https://doi.org/10.7554/eLife.06346.014
Figure 6 with 2 supplements
Serotonergic neuron background firing rates signal graded value.

(A) Median (horizontal line), interquartile range (box), and 1.5 times interquartile range (whiskers) of pre-trial firing rates during reward (black), neutral (gray), and punishment (orange) blocks. …

https://doi.org/10.7554/eLife.06346.015
Figure 6—figure supplement 1
Behavioral task.

(A) Structure of individual trials. (B) Average lick rate for all animals during each trial type.

https://doi.org/10.7554/eLife.06346.016
Figure 6—figure supplement 2
(A) Area under the ROC curve for reward, air-puff punishment, and quinine punishment trials for 21 serotonergic neurons.

(B) Area under the ROC curve for the punishment period for quinine vs air-puff punishments. Pearson correlation with significance test is shown. (C) Mean ± S.E.M. firing rate of serotonergic neurons …

https://doi.org/10.7554/eLife.06346.017
Serotonergic neurons signal value, not salience, in response to the CS.

(A) Mean ± S.E.M. firing rate of serotonergic neurons during all three trial conditions. (B) Mean ± S.E.M. firing rate during the CS epoch (region bounded by dashed lines in A) for each trial …

https://doi.org/10.7554/eLife.06346.018
Figure 8 with 2 supplements
A population of unidentified neurons is more or less active during blocks of reward trials than punishment trials.

(A) Mean ± S.E.M. firing rates of three example neurons during reward trials (black) and punishment trials (orange). Note the higher pre-trial firing rate during reward trials than punishment trials …

https://doi.org/10.7554/eLife.06346.019
Figure 8—figure supplement 1
Response profiles across all neurons and all trial types.

The figure shows the heterogeneity of unidentified neuron responses relative to serotonergic neurons. Area under the ROC curve for reward (left) and punishment trials (right) for each neuron. …

https://doi.org/10.7554/eLife.06346.020
Figure 8—figure supplement 2
Serotonergic neurons cannot be identified based on firing properties in this data set.

(A) Firing rate vs spike duration with marginal density histograms. Serotonergic neurons had significantly longer spike duration than unidentified neurons (Wilcoxon rank sum test, p < 0.05). (B) …

https://doi.org/10.7554/eLife.06346.021

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