Targets of Circadian Clock Neurons Influence Core Clock Parameters

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bioRxiv. 2025 Jul;. doi: https://doi.org/10.1101/2025.01.30.635801

Targets of Circadian Clock Neurons Influence Core Clock Parameters Rubin Lab

Scholz-Carson E, Iyer AR, Nern A, Ewer J, Fernandez MP

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Abstract

Neuronal connectivity in the circadian clock network is essential for robust endogenous timekeeping. In the Drosophila circadian clock network, the four pairs of small ventral lateral neurons (sLNvs) serve as main pacemakers. Peptidergic communication via sLNv, which release the key output neuropeptide, Pigment Dispersing Factor (PDF), has been well characterized. In the absence of PDF, flies become largely arrhythmic, similar to the phenotype associated with the loss of the mammalian circadian peptide, VIP. In contrast, little is known about the role of the synaptic connections that sLNvs form with downstream neurons. Connectomic analyses revealed that despite their role as key pacemaker neurons within the clock network, the sLNvs form few connections with other clock neurons. However, they form strong synaptic connections with a small group of previously uncharacterized neurons, SLP316, which in turn synapse onto dorsal clock neurons. Here, we show that silencing SLP316 neurons via tetanus toxin (TNT) expression shortens the free-running period, whereas hyper-exciting them by expressing the constitutively open Na[+] channel, NaChBac, results in period lengthening. Under light-dark cycles, silencing SLP316 neurons also causes lower daytime activity and higher daytime sleep. Our results revealed that the main postsynaptic partners of the Drosophila pacemaker neurons are a non-clock neuronal cell type that regulates the timing of sleep and activity.

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Targets of Circadian Clock Neurons Influence Core Clock Parameters

Abstract

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