Inutsuka, A. | Search bioRxiv

bioRxiv2026

Melanin-concentrating hormone inhibits PVN oxytocin neurons through a barium-sensitive inwardly rectifying potassium channels and MCH-neuron ablation alters pup-directed aggression

Interactions between melanin-concentrating hormone (MCH) neurons and oxytocin neurons are crucial for parental care. Whole-cell patch-clamp recordings demonstrated that MCH inhibits paraventricular hypothalamic nucleus (PVN)-oxytocin neurons through activation of barium-sensitive inwardly rectifying potassium channels, potentially G-protein coupled inwardly rectifying potassium channels, and pup-directed aggression was positively related to loss of MCH neurons. Our findings offer a glimpse into the neural mechanisms underlying the evolutionary regulation of offspring caregiving and abuse in males.

neuroscience↗

bioRxiv2019

Dissociating orexin-dependent and -independent functions of orexin neurons using novel orexin-Flp knock-in mice

Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. Thus, it is important to disambiguate orexin peptide-dependent and -independent physiological functions of orexin neurons. To attain this, we generated a novel orexin-flippase (Flp) knock-in (KI) mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was completely knock-out (KO) in KI/KI homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, activation of orexin neurons without orexin caused a significant increase in the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.

neuroscience↗