Salient experiences are represented by unique transcriptional signatures in the mouse brain
- The Hebrew University of Jerusalem, Israel
- Weizmann Institute of Science, Israel
- Ben-Gurion University of the Negev, Israel
- Vanderbilt University School of Medicine, United States
Abstract
It is well established that inducible transcription is essential for the consolidation of salient experiences into long-term memory. However, whether inducible transcription relays information about the identity and affective attributes of the experience being encoded, has not been explored. To this end, we analyzed transcription induced by a variety of rewarding and aversive experiences, across multiple brain regions. Our results describe the existence of robust transcriptional signatures uniquely representing distinct experiences, enabling near-perfect decoding of recent experiences. Furthermore, experiences with shared attributes display commonalities in their transcriptional signatures, exemplified in the representation of valence, habituation and reinforcement. This study introduces the concept of a neural transcriptional code, which represents the encoding of experiences in the mouse brain. This code is comprised of distinct transcriptional signatures that correlate to attributes of the experiences that are being committed to long-term memory.
Article and author information
Author details
Funding
Israel Science Foundation (Personal Grant 393/12 & I-CORE 1796/12)
- Ami Citri
The Lady Davis Postdoctoral Fellowship (Postdoctoral stipend)
- Bogna Marta Ignatowska-Jankowska
German-Israeli Foundation for Scientific Research and Development (Young Investigator Award 2299-2291.1./2011)
- Ami Citri
Brain and Behavior Research Foundation (Young Investigator Award #18795)
- Ami Citri
Canadian Institute for Advanced Research (Research Support)
- Ami Citri
Binational United-States Israel Research Foundation (Research Grant #2011266)
- Ami Citri
Milton Rosenbaum Research Foundation (Research Grant)
- Ami Citri
National Institutes for Psychobiology in Israel (Research Grant 109-15-16)
- Ami Citri
Shimon Peres Postdoctoral Award (Postdoctoral stipend)
- Bogna Marta Ignatowska-Jankowska
ELSC Postdoctoral Award (Postdoctoral stipend)
- Bogna Marta Ignatowska-Jankowska
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#NS-13-13895-3 ; NS-15-14668-3 ; NS-14-14088-3 ; NS-15-14312-3 ; NS-15-14348-3) of the Hebrew University of Jerusalem. The protocol was approved by the Committee on the Ethics of Animal Experiments of the Hebrew University. Every effort was made to minimize suffering.
Copyright
© 2018, Mukherjee et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,024
- views
-
- 1,075
- downloads
-
- 37
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Salient experiences are represented by unique transcriptional signatures in the mouse brain
eLife 7:e31220.
https://doi.org/10.7554/eLife.31220
Further reading
-
- Neuroscience
At many vertebrate synapses, presynaptic functions are tuned by expression of different Cav2 channels. Most invertebrate genomes contain only one Cav2 gene. The Drosophila Cav2 homolog, cacophony (cac), induces synaptic vesicle release at presynaptic active zones (AZs). We hypothesize that Drosophila cac functional diversity is enhanced by two mutually exclusive exon pairs that are not conserved in vertebrates, one in the voltage sensor and one in the loop binding Caβ and Gβγ subunits. We find that alternative splicing in the voltage sensor affects channel activation voltage. Only the isoform with the higher activation voltage localizes to AZs at the glutamatergic Drosophila larval neuromuscular junction and is imperative for normal synapse function. By contrast, alternative splicing at the other alternative exon pair tunes multiple aspects of presynaptic function. While expression of one exon yields normal transmission, expression of the other reduces channel number in the AZ and thus release probability. This also abolishes presynaptic homeostatic plasticity. Moreover, reduced channel number affects short-term plasticity, which is rescued by increasing the external calcium concentration to match release probability to control. In sum, in Drosophila alternative splicing provides a mechanism to regulate different aspects of presynaptic functions with only one Cav2 gene.
-
- Neuroscience
Sleep loss increases AMPA-synaptic strength and number in the neocortex. However, this is only part of the synaptic sleep loss response. We report an increased AMPA/NMDA EPSC ratio in frontal-cortical pyramidal neurons of layers 2–3. Silent synapses are absent, decreasing the plastic potential to convert silent NMDA to active AMPA synapses. These sleep loss changes are recovered by sleep. Sleep genes are enriched for synaptic shaping cellular components controlling glutamate synapse phenotype, overlap with autism risk genes, and are primarily observed in excitatory pyramidal neurons projecting intra-telencephalically. These genes are enriched with genes controlled by the transcription factor, MEF2c, and its repressor, HDAC4. Sleep genes can thus provide a framework within which motor learning and training occur mediated by the sleep-dependent oscillation of glutamate-synaptic phenotypes.
