Delaram Poormoghadam & Valentina Rumanova

Benchmarking the pre-autonomic neurons

The hypothalamic paraventricular nucleus (PVN) is a highly complex brain region that is crucial for homeostatic regulation through neuroendocrine signaling, outflow of the autonomic nervous system, and projections to other brain areas. In the past years, single-cell datasets of the hypothalamus have contributed immensely to the current understanding of the diverse hypothalamic cellular composition. While the PVN has been adequately classified functionally, its molecular classification is currently still insufficient. To address this, we created a detailed atlas of PVN transcriptomic cell types by integrating various PVN single-cell datasets into a recently published hypothalamus single-cell transcriptome atlas. To characterize the preautonomic functional population, we integrated a single-cell retrograde tracing study of spinally projecting pre-autonomic neurons into our PVN atlas. We identify these (pre-sympathetic) neurons to co-cluster with the Adarb2+ clusters in our dataset. We validated our findings with retrograde tracings and immunofluorescent stainings. In conclusion, our study presents a detailed overview of the transcriptomic cell types of the murine PVN and provides a first attempt to resolve functionality for the identified populations.

Dopamine D1 receptors in the central Clock

Organisms evolved internal clocks to adapt to environmental changes. In mammals, the central brain clock is in the hypothalamus, specifically the suprachiasmatic nuclei (SCN). The SCN synchronizes nearly all internal rhythms with a period of approx. 24 hours. These circadian rhythms are entrained to the exact 24-hour rhythm of the environment by photic cues (light) and non-photic cues (e.g., eating and exercise). Unfortunately, modern lifestyle, including shift work and nighttime light exposure, causes misalignment between these cues, disrupting the circadian timing system. Many studies have associated this so-called chronodisruption with cardiometabolic diseases, but mechanisms are unclear. We propose that dopamine could be a non-photic signal providing feedback to the SCN about the organism’s metabolic state.