MicroRNA expression is altered in lateral septum across reproductive stages.

MicroRNAs (miRNAs) inhibit RNA targets and may contribute to postpartum central nervous system (CNS) gene expression changes, although this has never been tested. In the present study, we directly evaluated miRNA levels using RNA sequencing during reproduction in female mice in the lateral septum (LS). We found the reliable and robust changes of miRNAs away from the virgin stage at the three other stages, namely pregnant, day 1 postpartum, and day 8 postpartum. For a given miRNA that was significantly different from the virgin condition in more than one group, the direction of change was always the same. Overall, we identified 32 upregulated miRNAs and 25 downregulated miRNAs that were consistently different from the virgin state. 'Arm switching' occurs for miR-433-3 and miR-7b. Unexpectedly, a third of upregulated miRNAs (relative to virgin) were highly localized within the 12qF1 region of chromosome 12 that includes the Dlk1-Dio3 gene cluster implicated in stem cell and neuronal differentiation. Over 1500 genes were targeted by multiple upregulated miRNAs with about 100 genes targeted by five or more miRNAs. Over 1000 genes were targeted by multiple downregulated miRNAs with about 50 genes targeted by five or more miRNAs. Half of the target genes were regulated by up and downregulated miRNAs, indicating homeostatic regulation. Transcriptional regulation was the most enriched pathway for genes linked to up or down regulated miRNAs. Other enriched pathways included protein kinase activity (e.g., MAP kinase), CNS development, axon guidance, neurotrophin signaling, neuron development/differentiation, and neurogenesis. Previously published postpartum LS gene expression changes were enrichment for LS miRNA targets, as expected. Surprisingly, postpartum gene expression changes from other regions were also enriched against LS miRNA targets, suggesting a core group of miRNAs may act across the CNS during reproduction. Together, we directly examine miRNAs and find significant alterations in the postpartum brain.

Sexually-motivated song is predicted by androgen-and opioid-related gene expression in the medial preoptic nucleus of male European starlings (Sturnus vulgaris).

Across vertebrates, communication conveys information about an individual's motivational state, yet little is known about the neuroendocrine regulation of motivational aspects of communication. For seasonally breeding songbirds, increases in testosterone in spring stimulate high rates of sexually-motivated courtship song, though not all birds sing at high rates. It is generally assumed that testosterone or its metabolites act within the medial preoptic nucleus (POM) to stimulate the motivation to sing. In addition to androgen receptors (ARs) and testosterone, opioid neuropeptides in the POM influence sexually-motivated song production, and it has been proposed that testosterone may in part regulate song by modifying opioid systems. To gain insight into a possible role for androgen-opioid interactions in the regulation of communication we examined associations between sexually-motivated song and relative expression of ARs, mu opioid receptors (muORs), and preproenkephalin (PENK) in the POM (and other regions) of male European starlings using qPCR. Both AR and PENK expression in POM correlated positively with singing behavior, whereas muOR in POM correlated negatively with song. Furthermore, the ratio of PENK/muOR expression correlated negatively with AR expression in POM. Finally, in the ventral tegmental area (VTA), PENK expression correlated negatively with singing behavior. Results support the hypothesis that ARs may alter opioid gene expression in POM to fine-tune singing to reflect a male's motivational state. Data also suggest that bidirectional relationships may exist between opioids and ARs in POM and song, and additionally support a role for opioids in the VTA, independent of AR activity in this region.