Circadian protein TIMELESS regulates synaptic plasticity and memory by modulating cAMP signaling
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ABSTRACT:
PROVIDER: PRJNA858471 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20169201_1.fastq.gz | Fastqsanger.gz | |||
| SRR20169201_2.fastq.gz | Fastqsanger.gz | |||
| SRR20169202_1.fastq.gz | Fastqsanger.gz | |||
| SRR20169202_2.fastq.gz | Fastqsanger.gz | |||
| SRR20169203_1.fastq.gz | Fastqsanger.gz |
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Project description:Regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of circadian genes on cellular and molecular mechanisms that influnce synaptic plasticity and cognitive function remain to be identified. Here, we show that conditional deletion of the circadian gene Timeless in the adult forebrain leads to an impairment in working and fear memory in mice. These cognitive phenotypes were accompanied with LTP attenuation of hippocampal Schaffer-collateral synapses. We discovered TIMELESS protein acts as a transcriptional factor regulating phosphodiesterase 4B (PDE4B) expression. Through Pde4b transcription, TIMELESS negatively regulates cAMP signaling to modulate AMPA receptor GluA1 function and fine-tune synaptic plasticity. Our data provide insights into the neuron-specific function of mammalian TIMELESS by defining a mechanism that regulates synaptic plasticity and cognitive function.
2023-04-17 | GSE208149 | GEO
Project description:The regulation of neurons by circadian clock genes is thought to contribute to the maintenance of neuronal functions that ultimately underlie animal behavior. However, the impact of specific circadian genes on cellular and molecular mechanisms controlling synaptic plasticity and cognitive function remains elusive. Here, we show that the expression of the circadian protein TIMELESS displays circadian rhythmicity in the mammalian hippocampus. We identify TIMELESS as a chromatin-bound protein that targets synaptic-plasticity-related genes such as phosphodiesterase 4B (Pde4b). By promoting Pde4b transcription, TIMELESS negatively regulates cAMP signaling to modulate AMPA receptor GluA1 function and influence synaptic plasticity. Conditional deletion of Timeless in the adult forebrain impairs working and contextual fear memory in mice. These cognitive phenotypes were accompanied by attenuation of hippocampal Schaffer-collateral synapse long-term potentiation. Together, these data establish a neuron-specific function of mammalian TIMELESS by defining a mechanism that regulates synaptic plasticity and cognitive function.
| S-EPMC10564971 | biostudies-literature
Project description:Rattus norvegicus Timeless, timeless circadian regulator [Source:RGD Symbol;Acc:620939], is differentially expressed in 26 experiment(s);
| ENSRNOG00000031916 | ExpressionAtlas
Project description:Rattus norvegicus Timeless, timeless circadian regulator [Source:RGD Symbol;Acc:620939], is expressed in 4 baseline experiment(s);
| ENSRNOG00000031916 | ExpressionAtlas
Project description:Equus caballus TIMELESS, timeless circadian regulator [Source:VGNC Symbol;Acc:VGNC:24108], is expressed in 1 baseline experiment(s);
| ENSECAG00000002892 | ExpressionAtlas
Project description:Homo sapiens TIMELESS, timeless circadian regulator [Source:HGNC Symbol;Acc:HGNC:11813], is expressed in 41 baseline experiment(s);
| ENSG00000111602 | ExpressionAtlas
Project description:Xenopus tropicalis timeless, timeless circadian regulator [Source:Xenbase;Acc:XB-GENE-985242], is differentially expressed in 1 experiment(s);
| ENSXETG00000021816 | ExpressionAtlas
Project description:Macaca mulatta TIMELESS, timeless circadian regulator [Source:VGNC Symbol;Acc:VGNC:78356], is expressed in 2 baseline experiment(s);
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Project description:Homo sapiens TIMELESS, timeless circadian regulator [Source:HGNC Symbol;Acc:HGNC:11813], is differentially expressed in 226 experiment(s);
| ENSG00000111602 | ExpressionAtlas
Project description:Circadian rhythms are present across almost all species and affect several physiological and behavioral aspects of living organisms. The evolutionary advantage conferred by these rhythms could be their anticipatory properties. In the nervous system, anticipation is particularly interesting due to the spatiotemporal constraints derived by the highly compartmentalized neuronal structure. Previous work has confirmed that 900 genes are expressed in the mouse forebrain in robustly rhythmic fashion, and 180 transcripts are equally robustly circadian at the synapse. Interestingly, mRNAs are found in higher amounts at the end of the dark phase, and decrease exponentially during the first hours of light. This pattern resembles the “sawtooth” pattern of homeostatic sleep pressure. To further characterize this phenotype we propose to compare the synaptic transcriptome of sleep deprived mice to its control base line. This work would shed light into the emerging field of synaptic RNA transport and translation and its regulatory inputs. Hopefully, the results will yield to two different findings: the circadian and activity potential to regulate synaptic transport of RNA and the classification of transcripts deferentially regulated by both processes.
2019-02-28 | E-MTAB-7347 | biostudies-arrayexpress