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Circadian protein TIMELESS regulates synaptic plasticity and memory by modulating cAMP signaling

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE208149 | GEO | 2023/04/17

REPOSITORIES: GEO

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Circadian protein TIMELESS regulates synaptic plasticity and memory by modulating cAMP signaling

Project description:Circadian protein TIMELESS regulates synaptic plasticity and memory by modulating cAMP signaling

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