Neuropeptides: The Evergreen Jack-of-All-Trades in Neuronal Circuit Development and Regulation.

Neuropeptides are key modulators of adult neurocircuits, balancing their sensitivity to both excitation and inhibition, and fine-tuning fast neurotransmitter action under physiological conditions. Here, we reason that transient increases in neuropeptide availability and action exist during brain development for synapse maturation, selection, and maintenance. We discuss fundamental concepts of neuropeptide signaling at G protein-coupled receptors (GPCRs), with a particular focus on how signaling at neuropeptide GPCRs could underpin neuronal morphogenesis.

Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3.

Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1/Onecut1/2 proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH) glutamate neurons through neuron navigator-2 (NAV2).

A hydrophobic groove in secretagogin allows for alternate interactions with SNAP-25 and syntaxin-4 in endocrine tissues.

Vesicular release of neurotransmitters and hormones relies on the dynamic assembly of the exocytosis/trans-SNARE complex through sequential interactions of synaptobrevins, syntaxins, and SNAP-25. Despite SNARE-mediated release being fundamental for intercellular communication in all excitable tissues, the role of auxiliary proteins modulating the import of reserve vesicles to the active zone, and thus, scaling repetitive exocytosis remains less explored. Secretagogin is a Ca-sensor protein with SNAP-25 being its only known interacting partner.

Transient expression of the neuropeptide galanin modulates peripheral‑to‑central connectivity in the somatosensory thalamus during whisker development in mice.

The significance of transient neuropeptide expression during postnatal brain development is unknown. Here, we show that galanin expression in the ventrobasal thalamus of infant mice coincides with whisker map development and modulates subcortical circuit wiring. Time-resolved neuroanatomy and single-nucleus RNA-seq identified complementary galanin (Gal) and galanin receptor 1 (Galr1) expression in the ventrobasal thalamus and the principal sensory nucleus of the trigeminal nerve (Pr5), respectively.