Biology subjects

Abruzzi, K.

Publications and source records attributed to Abruzzi, K..

4 recordsLinked to original sources

bioRxiv2024

Novel clock neuron subtypes regulate temporal aspects of sleep

Circadian neurons within animal brains orchestrate myriad physiological processes and behaviors, But the contribution of these neurons to the regulation of sleep is not well understood. To address this deficiency, we leveraged single-cell RNA sequencing to generate a new and now comprehensive census of transcriptomic cell types of Drosophila clock neurons. We focused principally on the enigmatic DN3s, which constitute about half of the 75 pairs of clock neurons in the fly brain and were previously almost completely uncharacterized. These DN3s are organized into 12 clusters with unusual gene expression features compared to the more well-studied clock neurons. We further show that different DN3 subtypes with distinct projection patterns promote sleep at specific times of the day through a common G protein-coupled receptor, TrissinR. Our findings indicate an intricate regulation of sleep behavior by clock neurons and highlight their remarkable diversity in gene expression, projection patterns and functional properties.

neuroscience↗

bioRxiv2022

Neural connectivity molecules best identify the heterogeneous clock and dopaminergic cell types in the Drosophila adult brain

Our recent single cell sequencing of most adult Drosophila circadian neurons indicated striking gene expression heterogeneity, about 2-3 cells per clock neuron group. To extend this characterization to other adult fly brain neurons, we used the identical plate-based methods to generate single cell data from a similar subset of dopaminergic neurons. To minimize batch effects and to apply an additional sequencing strategy, we also assayed these two populations together with 10X Chromium. An unsupervised clustering algorithm indicates that dopaminergic neurons are comparably heterogeneous, suggesting that the transcriptomic diversity of adult fly brain neurons parallels its EM connectome. The results here further indicate that connectivity molecules like cell surface molecules best characterize all neuron groups. We suggest that these surprising features are general and make major contributions to neuronal identity and connectivity of the adult central brain as well as underlie the complex behavioral repertoire of Drosophila.

neuroscience↗

bioRxiv2021

Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G-Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single cell sequencing indicates that they are not only differentially expressed but also define clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy with a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a novel role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

neuroscience↗

bioRxiv2018

Allatostatin C/AstC-R2 is a Novel Pathway to Modulate Circadian Activity Pattern in Drosophila

Six neuropeptides are expressed within the Drosophila brain circadian network. Our previous mRNA profiling suggested that AllatostatinC is a seventh neuropeptide and specifically expressed in dorsal clock neurons (DN1s). Our results here show that AstC is indeed expressed in DN1s, where it oscillates. AstC is also expressed in two less well-characterized circadian neuronal clusters, the DN3s and lateral posterior neurons (LPNs). Behavioral experiments indicate that clock neuron-derived AstC is required to mediate evening locomotor activity under short (winter-like) photoperiods. The AstC-Receptor 2 (AstC-R2) is expressed in LNds, the clock neurons that drive evening locomotor activity, and AstC-R2 is required in these neurons to modulate the same short photoperiod evening phenotype. Ex vivo calcium imaging indicates that AstC directly inhibits a single LNd neuron. The results suggest that a novel AstC/AstC-R2 signaling pathway, from dorsal circadian neurons to an LNd, regulates the behavioral response to changing photoperiod in Drosophila.

neuroscience↗