Cell sensory neuron response is achieved through transcriptome changes

Written | In November, the different tastes smelled by animals will be detected by primary neurons, and then the information of the odor will be sent to the brain circuit to distinguish, thereby establishing the response to different odors
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Most sensory neurons undergo rapid, millisecond-to-second sensory adaptation, which is critical for animals to recognize food or dangerous situations and respond immediately
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However, it is not clear how sensory neurons respond and adapt to environmental odor cues on a longer time scale
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The general view is that Odor-odor receptors are a universal mechanism for animals to adapt to different environmental cues.
The brain uses the obtained information to decode and decide the next action [1,2]
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There are also views that have proposed that Activity-dependent transcription [3] may be a way for animals to adapt to long-term environmental changes.
For example, mature brain neurons use synaptic proteins and ion channels to regulate transcription, so as to adjust transcription over a period of time.
The firing rate of neurons is stably maintained within
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In order to uncover the sensory neuron response mechanism of long-term animal adaptation to odor, on December 7, 2021, the research group of Sandeep Robert Datta of Harvard University School of Medicine published a paper entitled A transcriptional rheostat couples past activity to future sensory responses, and found environmental cues The specific mechanism that animals adapt to the environment through changes in transcriptional landscape and functional gene expression during changes
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There are more than 1,000 different olfactory neurons in the brain of mice, and each neuron can be distinguished by the different olfactory neuron receptors it expresses [4]
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Olfactory neuron receptors are G protein-coupled receptors, which can transform olfactory signals into calcium ion signals to promote the generation of action potentials
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Olfactory neurons and cerebral cortex adapt to the environment on a time scale of minutes
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Therefore, olfactory neuron receptors can accurately reflect the reflection characteristics of olfactory neurons
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However, whether environment-dependent transcriptional changes will adapt to the specific olfactory response of olfactory neuron receptors is still unknown
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Figure 1 Large-scale single-cell RNA-seq and classification of sensory neurons.
To this end, the authors hope to use single-cell RNA-seq to detect large-scale transcriptional changes in different known olfactory neurons, thereby It responds to how olfactory neurons adapt to environmental cues when the environment changes (Figure 1)
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First, the authors performed single-cell RNA-seq on 770,000 mature sensory neurons in the mouse brain.
The classification of sensory neurons mainly depends on different cell markers and the location of the brain area
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The results of single-cell sequencing confirmed that the transcriptome of sensory neurons has a specific type and can be specifically labeled by the expressed sensory neuron receptors
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Subsequently, the authors described the response of caged mice to long-term environmental cues based on the single-cell RNA-seq map obtained
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To this end, the authors proposed the concept of Gene expression programs (GEPs), which classifies 1,350 highly variable genes
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In general, mouse Bacillus neuron gene expression programs can be divided into five types of identity-related gene expression programs and two types of activity-related gene expression programs
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The two types of activity-related gene expression programs are divided into high expression and low expression, and the difference between the two changes is the change in gene expression brought about by environmental clues, that is, the transcription landscape
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Consistent with changes in environmental cues, the systemic environmental state score changes in the transcriptome of sensory neurons can reflect neuronal activity since the environment
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The specific interaction difference between each sensory neuron receptor and the environment drives the activity of each sensory neuron, which in turn specifies the specific levels of different gene expression in the high-expressed gene expression program as well as the low-expressed gene expression program
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In order to test whether the linked changes in functional gene expression can specifically show the response of each odor, the authors used Act-seq to detect olfactory epithelial cells
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Act-seq is a variant of single-cell RNA-seq sequencing, which can interpret neural activity as rapid changes in gene expression [5]
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The authors found that Act-seq can accurately identify gene expression changes in sensory neurons in mice after exposure to volatile odorants
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If functional gene expression does play a causal role in the sensory response of mice, then increasing or decreasing the environmental status score can be used to predict changes in gene expression after changes in odor cues
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Therefore, the authors conducted an obstruction-dependent experiment.
Single-cell RNA-seq and Act-seq were performed on the sensory neurons of the blocked nostril and the natural state of the nostril.
The authors found that transient nostril blockage will use sensory neuron receptors.
The way of dependence reduces the environmental status score, but it does not affect the structural relevance of functional genes
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Furthermore, the authors further proved this by in vivo imaging of neurons in the body
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Therefore, long-term odor changes do not only depend on the affinity between sensory neurons and corresponding receptors, but more on the transcriptional changes of functional genes
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Figure 3 Working model.
In general, the work found that mouse olfactory neurons reflect the response of sensory neurons to odors over a longer period of time through unique, olfactory receptor-dependent specific transcriptome changes (Figure 3 )
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This transcriptional rheostat effect is systemic, which can support the adaptation of odor environmental cues.
Different sensory neuron subtypes can convert odor into continuous changes in the expression levels of multiple functional genes, thereby dynamically Adapt to the new environment
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Original link: https://doi.
org/10.
1016/j.
cell.
2021.
11.
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Computation in the Olfactory System.
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3 Ee-Lynn, Yap, Michael & Neuron, GJ Activity-Regulated Transcription: Bridging the Gap between Neural Activity and Behavior.
(2018).
4 Monahan, K.
, Lomvardas, SJAR o.
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& Biology, D.
Monoallelic Expression of Olfactory Receptors.
31, 721 (2015).
5 Wu, YE, Pan, L.
, Zuo, Y.
, Li, X.
& Hong, W.
Detecting Activated Cell Populations Using Single-Cell RNA-Seq.
Neuron 96, 313-329.
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