A transcriptional rheostat couples past activity to future sensory responses

Tatsuya Tsukahara; David H. Brann; Stan L. Pashkovski; Grigori Guitchounts; Thomas Bozza; Sandeep Robert Datta

doi:10.1016/j.cell.2021.11.022

A transcriptional rheostat couples past activity to future sensory responses

Tatsuya Tsukahara, David H. Brann, Stan L. Pashkovski, Grigori Guitchounts, Thomas Bozza, Sandeep Robert Datta^*

^*Corresponding author for this work

Neurobiology

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.

Original language	English (US)
Pages (from-to)	6326-6343.e32
Journal	Cell
Volume	184
Issue number	26
DOIs	https://doi.org/10.1016/j.cell.2021.11.022
State	Published - Dec 22 2021

Funding

We thank John McGann and Matthew Grubb for technical advice on naris occlusion; Venkatesh Murthy, Dima Rinberg, and Catherine Dulac for mice; and Kelsey Tyssowski, Vanessa Ruta, Rachel Wilson, Bernardo Sabatini, David Ginty, Michael Greenberg, Piali Sengupta, and the Datta lab for useful comments on the manuscript. We thank Neha Bhagat for laboratory assistance and Janet Wallace for administrative assistance. We thank the Bauer Core Facility at Harvard University for sequencing and the Flow Cytometry Core at Beth Israel Deaconess Medical Center. Portions of this research were conducted on the O2 High Performance Compute Cluster at Harvard Medical School. Illustrations were created in part with BioRender.com and Vecteezy.com . S.R.D. is supported by NIH grants R011DC016222 and U19 NS112953 and by grants from the Simons Collaboration on the Global Brain , the Brain Research Foundation , and the Tan Yang Center at Harvard Medical School . T.T. is supported by postdoctoral fellowships from the Japan Society for the Promotion of Science , the Louis Perry Jones Fund , and the Tan Yang Center . D.H.B. is supported by an NSF Graduate Research Fellowship and by NIH grant F31DC019017 . We thank John McGann and Matthew Grubb for technical advice on naris occlusion; Venkatesh Murthy, Dima Rinberg, and Catherine Dulac for mice; and Kelsey Tyssowski, Vanessa Ruta, Rachel Wilson, Bernardo Sabatini, David Ginty, Michael Greenberg, Piali Sengupta, and the Datta lab for useful comments on the manuscript. We thank Neha Bhagat for laboratory assistance and Janet Wallace for administrative assistance. We thank the Bauer Core Facility at Harvard University for sequencing and the Flow Cytometry Core at Beth Israel Deaconess Medical Center. Portions of this research were conducted on the O2 High Performance Compute Cluster at Harvard Medical School. Illustrations were created in part with BioRender.com and Vecteezy.com. S.R.D. is supported by NIH grants R011DC016222 and U19 NS112953 and by grants from the Simons Collaboration on the Global Brain, the Brain Research Foundation, and the Tan Yang Center at Harvard Medical School. T.T. is supported by postdoctoral fellowships from the Japan Society for the Promotion of Science, the Louis Perry Jones Fund, and the Tan Yang Center. D.H.B. is supported by an NSF Graduate Research Fellowship and by NIH grant F31DC019017. T.T. D.H.B. and S.R.D. designed the study and interpreted the data. T.T. and D.H.B. performed and analyzed scRNA-seq experiments; T.T. D.H.B. and G.G. performed optogenetic stimulation experiments; and T.T. D.H.B. and S.L.P. performed and analyzed functional imaging experiments. T.B. provided resources and assisted in experimental design and interpretation. T.T. D.H.B. and S.R.D. wrote the manuscript with input from all authors. The authors declare no competing interests.

Keywords

Act-seq
adaptation
functional imaging
gene expression programs
homeostasis
odor coding
odorant receptor
olfaction
sensory neurons
single-cell RNA sequencing
transcription

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2021.11.022

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title = "A transcriptional rheostat couples past activity to future sensory responses",

abstract = "Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.",

keywords = "Act-seq, adaptation, functional imaging, gene expression programs, homeostasis, odor coding, odorant receptor, olfaction, sensory neurons, single-cell RNA sequencing, transcription",

author = "Tatsuya Tsukahara and Brann, {David H.} and Pashkovski, {Stan L.} and Grigori Guitchounts and Thomas Bozza and Datta, {Sandeep Robert}",

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AU - Brann, David H.

AU - Pashkovski, Stan L.

AU - Guitchounts, Grigori

AU - Bozza, Thomas

AU - Datta, Sandeep Robert

PY - 2021/12/22

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N2 - Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.

AB - Animals traversing different environments encounter both stable background stimuli and novel cues, which are thought to be detected by primary sensory neurons and then distinguished by downstream brain circuits. Here, we show that each of the ∼1,000 olfactory sensory neuron (OSN) subtypes in the mouse harbors a distinct transcriptome whose content is precisely determined by interactions between its odorant receptor and the environment. This transcriptional variation is systematically organized to support sensory adaptation: expression levels of more than 70 genes relevant to transforming odors into spikes continuously vary across OSN subtypes, dynamically adjust to new environments over hours, and accurately predict acute OSN-specific odor responses. The sensory periphery therefore separates salient signals from predictable background via a transcriptional rheostat whose moment-to-moment state reflects the past and constrains the future; these findings suggest a general model in which structured transcriptional variation within a cell type reflects individual experience.

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KW - functional imaging

KW - gene expression programs

KW - homeostasis

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KW - sensory neurons

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KW - transcription

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A transcriptional rheostat couples past activity to future sensory responses

Abstract

Funding

Keywords

ASJC Scopus subject areas

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