Widespread posttranscriptional regulation of cotransmission

While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters...

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Bibliographic Details
Published in:Science advances 2023-06, Vol.9 (22), p.eadg9836-eadg9836
Main Authors: Chen, Nannan, Zhang, Yunpeng, Rivera-Rodriguez, Emmanuel J, Yu, Albert D, Hobin, Michael, Rosbash, Michael, Griffith, Leslie C
Format: Article
Language:English
Subjects:
Cellular Neuroscience
Cholinergic Agents
MicroRNAs - genetics
MicroRNAs - metabolism
Neurons - metabolism
Neuroscience
SciAdv r-articles
Sleep - physiology
Synaptic Transmission - genetics
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Summary:While neurotransmitter identity was once considered singular and immutable for mature neurons, it is now appreciated that one neuron can release multiple neuroactive substances (cotransmission) whose identities can even change over time. To explore the mechanisms that tune the suite of transmitters a neuron releases, we developed transcriptional and translational reporters for cholinergic, glutamatergic, and GABAergic signaling in . We show that many glutamatergic and GABAergic cells also transcribe cholinergic genes, but fail to accumulate cholinergic effector proteins. Suppression of cholinergic signaling involves posttranscriptional regulation of cholinergic transcripts by the microRNA miR-190; chronic loss of miR-190 function allows expression of cholinergic machinery, reducing and fragmenting sleep. Using a "translation-trap" strategy, we show that neurons in these populations have episodes of transient translation of cholinergic proteins, demonstrating that suppression of cotransmission is actively modulated. Posttranscriptional restriction of fast transmitter cotransmission provides a mechanism allowing reversible tuning of neuronal output.
ISSN:2375-2548
2375-2548
DOI:10.1126/SCIADV.ADG9836