Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter.

eScholarship, University of California 2023-06-01

The transcriptional effects of SSRIs and other serotonergic drugs remain unclear, in part due to the heterogeneity of postsynaptic cells, which may respond differently to changes in serotonergic signaling. Relatively simple model systems such as Drosophila afford more tractable microcircuits in which to investigate these changes in specific cell types. Here, we focus on the mushroom body, an insect brain structure heavily innervated by serotonin and comprised of multiple different but related subtypes of Kenyon cells. We use fluorescence-activated cell sorting of Kenyon cells, followed by either bulk or single-cell RNA sequencing to explore the transcriptomic response of these cells to SERT inhibition. We compared the effects of two different Drosophila Serotonin Transporter (dSERT) mutant alleles as well as feeding the SSRI citalopram to adult flies. We find that the genetic architecture associated with one of the mutants contributed to significant artefactual changes in expression. Comparison of differential expression caused by loss of SERT during development versus aged, adult flies, suggests that changes in serotonergic signaling may have relatively stronger effects during development, consistent with behavioral studies in mice. Overall, our experiments revealed limited transcriptomic changes in Kenyon cells, but suggest that different subtypes may respond differently to SERT loss-of-function. Further work exploring the effects of SERT loss-of-function in other circuits may be used help to elucidate how SSRIs differentially affect a variety of different neuronal subtypes both during development and in adults.

Neurons; Animals; Drosophila; Citalopram; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors; Neurosciences; Genetics; Underpinning research; 1.1 Normal biological development and functioning; Aetiology; 2.1 Biological and endogenous factors; Generic health relevance; Clinical Sciences; Public Health and Health Services; Psychology; article

application/pdf
Translational psychiatry vol 13, iss 1, 226 2158-3188

CDLER oai:escholarship.org:ark:/13030/qt3h73v2wk
qt3h73v2wk
https://escholarship.org/uc/item/3h73v2wk
https://escholarship.org/
1391575965

UC MASS DIGITIZATION
From OAIster®, provided by the OCLC Cooperative.

edsoai.on1391575965