Salient experiences are represented by unique transcriptional signatures in the mouse brain

  1. Diptendu Mukherjee
  2. Bogna Marta Ignatowska-Jankowska
  3. Eyal Itskovits
  4. Ben Jerry Gonzales
  5. Hagit Turm
  6. Liz Izakson
  7. Doron Haritan
  8. Noa Bleistein
  9. Chen Cohen
  10. Ido Amit
  11. Tal Shay
  12. Brad Grueter
  13. Alon Zaslaver
  14. Ami Citri  Is a corresponding author
  1. The Hebrew University, Israel
  2. Weizmann Institute of Science, Israel
  3. Ben-Gurion University of the Negev, Israel
  4. Vanderbilt University School of Medicine, United States
  5. Canadian Institute for Advanced Research, Canada
3 figures and 16 additional files

Figures

Figure 1 with 6 supplements
Transcriptional signatures representing recent experience.

(A) Schematic of experimental paradigm for cocaine sensitization. Mice were exposed to cocaine (i.p., 20 mg/kg) or saline, either acutely, repeatedly or re-exposed following abstinence (challenge), …

https://doi.org/10.7554/eLife.31220.003
Figure 1—figure supplement 1
Boundaries of dissected structures.

Shaded regions in blue represent areas cut out from 400 µm slices for LCtx (limbic cortex), NAc (nucleus accumbens), DS (dorsal striatum), Amy (amygdala), LH (lateral hypothalamus), and Hipp …

https://doi.org/10.7554/eLife.31220.004
Figure 1—figure supplement 2
Acute, repeated and challenge cocaine experiences induce distinct transcriptional programs across brain structures.

(A) Schematic of the experimental paradigm. (B) Average transcriptional induction of 78 genes one hour following acute, repeated or challenge cocaine experiences in six brain nuclei [LCtx: limbic …

https://doi.org/10.7554/eLife.31220.005
Figure 1—figure supplement 3
Time course of transcriptional induction of a minimal set of markers representing cocaine-induced transcriptional dynamics.

(A) Schematic of the experimental paradigms. (B) Arc, Egr2, Egr4, Fos and Fosb induction (0, 1, 2, 4 hr) following acute, repeated and challenge cocaine in seven brain nuclei (LCtx: limbic cortex, …

https://doi.org/10.7554/eLife.31220.006
Figure 1—figure supplement 4
Transcriptional representation of LiCl experience.

(A) Schematic of experimental paradigm. (B) Comparison of average transcriptional induction of 78 genes following acute LiCl (n = 5) or repeated LiCl (n = 4) at 1 hr time point, in limbic cortex …

https://doi.org/10.7554/eLife.31220.007
Figure 1—figure supplement 5
Characterization of repeated saline exposures illustrates the effect of habituation on induced transcription.

(A) Experimental paradigm for i.p. saline injections. (B) Bar graphs demonstrating the transcriptional induction of Arc, Egr2, Egr4 and Fos in the LCtx, NAc, and DS (limbic cortex, nucleus …

https://doi.org/10.7554/eLife.31220.008
Figure 1—figure supplement 6
Characterization of the transcription induced by acute and repeated saline experiences.

(A) Schematic of the experimental paradigm of i.p. injections of saline. (B) Expression matrix of the transcriptional induction of IEGs following acute or repeated saline experiences. Each column …

https://doi.org/10.7554/eLife.31220.009
Figure 2 with 5 supplements
Salient experiences are represented by unique transcriptional signatures.

(A) Schematic of experimental paradigms. Experiences analyzed include saline (acute and repeated); foot shock (acute shock and no-shock controls exposed to the same environment); LiCl (acute and …

https://doi.org/10.7554/eLife.31220.010
Figure 2—figure supplement 1
Low variability of the individual transcriptional representations of recent experience.

Radar plots representing the transcriptional induction of Arc, Egr2, Egr4 and Fos, in seven brain nuclei [LCtx: limbic cortex (n = 4–14), NAc: nucleus accumbens (n = 4–14), DS: dorsal striatum (n = 4…

https://doi.org/10.7554/eLife.31220.011
Figure 2—figure supplement 2
Transcriptional representation of negative valence in the amygdala.

Comparison of average transcriptional induction of Arc, Egr2, Egr4 and Fos in the LCtx, NAc, DS, Amy, LH and Hipp, 1 hr following acute exposure to the fear-conditioning chamber (no shock) or brief …

https://doi.org/10.7554/eLife.31220.012
Figure 2—figure supplement 3
Transcriptional representation of habituation and reinforcement.

Comparison of the transcriptional profiles induced by acute and repeated aversive (LiCl) and rewarding (cocaine and sucrose) experiences reveal distinctions and commonalities in the encoding of an …

https://doi.org/10.7554/eLife.31220.013
Figure 2—figure supplement 4
Reinstatement of feeding is represented by robust transcriptional dynamics.

(A) Schematic of experimental paradigm for reinstatement of feeding. Mice were continuously fed or food deprived for 18 hr, followed by analysis of transcription at 0, 1, 2, 4 hr after reinstatement …

https://doi.org/10.7554/eLife.31220.014
Figure 2—figure supplement 5
Reinstatement of feeding is represented by robust transcriptional dynamics.

Comparison of transcriptional induction of Arc, Egr2, Egr4 and Fos, at 0 (deprived) and 1 hr following reinstatement of feeding (re-fed), and continuously fed mice (fed control) across five brain …

https://doi.org/10.7554/eLife.31220.015
Figure 3 with 2 supplements
Decoding the recent experience of individual mice from minimal transcriptional signatures.

(A) Confusion matrix representing the classification accuracy (90.7%) of decoding the recent experience of individual mice based on 25 features. Efficiency is scaled from blue to green, with bright …

https://doi.org/10.7554/eLife.31220.016
Figure 3—figure supplement 1
Decoding the recent experience of individual mice from averaged gene expression across different brain regions.

Confusion matrix representing the classification accuracy (55.6%) of decoding the recent experience of individual mice based on averaged transcriptional induction of Arc, Egr2, Egr4, Fos and Fosb) …

https://doi.org/10.7554/eLife.31220.017
Figure 3—figure supplement 2
Feature selection to identify the features contributing most significantly to decoding.

(A, E) Selection of features (expression of IEG in a brain structure) with the highest potential to contribute to the classification of recent experiences (‘support’). Support was defined by running …

https://doi.org/10.7554/eLife.31220.018

Additional files

Source Code 1

Classfication Tests_averageGenes

https://doi.org/10.7554/eLife.31220.019
Source Code 2

Classfication Tests_averageRegions

https://doi.org/10.7554/eLife.31220.020
Source Code 3

Classfication Tests_pcaOverRegions

https://doi.org/10.7554/eLife.31220.021
Source Code 4

ClassificationAndConfusionMatrices_confMat

https://doi.org/10.7554/eLife.31220.022
Source Code 5

Classification And Confusion Matrices_knnEvaluate

https://doi.org/10.7554/eLife.31220.023
Source Code 6

Feature Selection RKNN_find Features

https://doi.org/10.7554/eLife.31220.024
Source Code 7

Feature Selection RKNN_find Interesting Genes

https://doi.org/10.7554/eLife.31220.025
Source Code 8

Features Selection Random Forest_DecisionTree

https://doi.org/10.7554/eLife.31220.026
Source Code 9

Linear Projections_RegionsScatter

https://doi.org/10.7554/eLife.31220.027
Source Code 10

Linear Projections

https://doi.org/10.7554/eLife.31220.028
Source Code 11

Randomization_permTest

https://doi.org/10.7554/eLife.31220.029
Supplementary file 1

Primer sequences and efficiency calculations.

https://doi.org/10.7554/eLife.31220.030
Supplementary file 2

Raw data.

https://doi.org/10.7554/eLife.31220.031
Supplementary file 3

Statistics.

https://doi.org/10.7554/eLife.31220.032
Supplementary file 4

Animal numbers

https://doi.org/10.7554/eLife.31220.033
Transparent reporting form
https://doi.org/10.7554/eLife.31220.034

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