Biology subjects

Tsuneoka, Y.

Publications and source records attributed to Tsuneoka, Y..

4 recordsLinked to original sources

bioRxiv2026

Sustained effect of MPOA Penk neurons underlies progression through consummatory mating behavior in male mice

Male rodent sexual behavior progresses from appetitive to consummatory mating, implying a sustained internal motivational state. Estrogen receptor 1 (Esr1)-expressing neurons in the medial preoptic area (MPOA) regulate discrete mating actions, but how motivational drive is sustained across mating remains unknown. Here, we identify an MPOA Esr1+ neuronal subtype marked by proenkephalin (Penk) that promotes the transition from mount to intromission. Male mice exhibited a bimodal progression to consummatory mating, and Penk-expressing neurons represented the predominant population recruited for consummatory behaviors. In sexually active males, Penk+ neurons exhibited sustained Ca{superscript 2} dynamics. Chemogenetic manipulation selectively enhanced female-directed consummatory behaviors without affecting intermale interactions. Optogenetic activation of Penk+ neurons or their terminals promoted consummatory behavior over a behaviorally relevant timescale. Thus, MPOA Penk+ neurons provide a circuit substrate for a sustained internal state that ensures successful mating progression.

neuroscience↗

bioRxiv2025

Maternal care during early development is necessary for the acquisition of a calming response to back stroking

In many mammals, early postnatal interactions between caregivers and offspring involve rich physical contact, including stroking, holding, and grooming. Offspring typically remain calm and close to the caregiver during such stimulation. Although these behaviors are thought to support emotional regulation and bonding during infancy, the underlying mechanisms and the role of prior experience remain unclear. Here, we demonstrate that back stroking induces a conserved calming response in both human infants and mouse pups, characterized by reduced movement and heart rate. In mouse pups, stroking further facilitated sleep onset, increased EEG delta power, and attenuated stress-induced corticosterone elevations. These sleep-promoting and stress-buffering effects were absent in artificially reared pups deprived of postnatal maternal contact, underscoring the importance of early tactile experience. Transcriptomic analysis revealed downregulation of the voltage-gated calcium channel subunit gene Cacna1b in the hypothalamus of artificially reared pups. Moreover, knockdown of hypothalamic Cacna1b in maternally reared pups abolished stroking-induced calming and sleep-promoting effects. This study identifies a conserved, experience-dependent calming response to affiliative tactile input, biologically embedded through plasticity, that supports physiological regulation and stress resilience during early development. Our results highlight that affiliative tactile sensation, like discriminative tactile sensation, depends on early experience to organize neural mechanisms regulating internal states. SignificanceEarly-life physical contact with caregivers is essential for healthy emotional and physiological development in mammals, but its underlying mechanisms remain unclear. We show that back stroking induces a conserved calming response in both human infants and mouse pups, reducing movement, heart rate, and promoting sleep. These effects depend on early tactile experience and are mediated by Cacna1b expression in the hypothalamus. Our findings identify a plastic, experience-dependent pathway through which affiliative tactile input modulates internal states, revealing how parental care supports stress resilience and sleep physiology during early development.

neuroscience↗

bioRxiv2023

Synaptic plasticity in the medial preoptic area of male mice encodes social experiences with female and regulates behavior toward young

A dramatic shift from aggressive infanticidal to paternal behaviors is an essential event for male mice after mating. While the central part of the medial preoptic area (cMPOA) has been shown to critically mediate the paternal behaviors in mice, how this brain region becomes activated by mating and subsequent interaction with pups has not been investigated. Here, we demonstrate that the reduction in inhibitory synaptic strength towards the cMPOA provided by posterior-dorsal medial amygdala (MePD) neurons is a key event for the post-mating behavioral shift in males. Consistent with this, we found optogenetic disinhibition of MeCartpt to the cMPOA synapses reduces male aggression towards pups. The cMPOA of paternal mice mediated pup-induced neural plastic changes in the bed nucleus of the stria terminalis. These findings provide possible functions of cMPOA neural circuits required for the reception to young in male mice.

zoology↗

bioRxiv2023

Whole brain mapping of orexin receptor mRNA expression visualized by branched in situ hybridization chain reaction

Orexins, which are produced within neurons of the lateral hypothalamic area, play a pivotal role in the regulation of various behaviors, including sleep/wakefulness, reward behavior, and energy metabolism, via orexin receptor type 1 (OX1R) and type 2 (OX2R). Despite the advanced understanding of orexinergic regulation of behavior at the circuit level, the precise distribution of orexin receptors in the brain remains unknown. Here, we develop a new branched in situ hybridization chain reaction (bHCR) technique to visualize multiple target mRNAs in a semiquantitative manner, combined with immunohistochemistry, which provided comprehensive distribution of orexin receptor mRNA and neuron subtypes expressing orexin receptors in mouse brains. Only a limited number of cells expressing both Ox1r and Ox2r were observed in specific brain regions, such as the dorsal raphe nucleus and ventromedial hypothalamic nucleus. In many brain regions, Ox1r-expressing cells and Ox2r-expressing cells belong to different cell types, such as glutamatergic and GABAergic neurons. Moreover, our findings demonstrated considerable heterogeneity in Ox1r- or Ox2r-expressing populations of serotonergic, dopaminergic, noradrenergic, cholinergic, and histaminergic neurons. The majority of orexin neurons did not express orexin receptors. This study provides valuable insights into the mechanism underlying the physiological and behavioral regulation mediated by the orexin system, as well as the development of therapeutic agents targeting orexin receptors. Significance statementThe neuropeptide orexin regulates sleep and other behaviors through its receptors, OX1R and OX2R, which are targets for the development of therapeutic agents for sleep and related disorders. However, the cellular distribution of orexin receptors in the brain is only partially known. We applied a newly developed branched in situ hybridization chain reaction (bHCR) technique and conducted a whole-brain mapping of orexin receptor mRNA expression in the brain with neuron subtype markers. Few cells expressed both OX1R and OX2R, and OX1R and OX2R were expressed in the different neuronal subtypes in many brain regions. This study fills an important gap in understanding and modulating the orexin system.

neuroscience↗