Biology subjects

Inada, K.

Publications and source records attributed to Inada, K..

7 recordsLinked to original sources

bioRxiv2026

A neuronal population in the bed nucleus of the stria terminalis mediating pup-directed aggression in male mice

The mammalian brain orchestrates a broad range of social behaviors, including interactions with conspecific young. Sexually inexperienced male mice typically exhibit pup-directed aggression, whereas fathers display caregiving behaviors. Although this behavioral transition provides a valuable framework for understanding life stage-dependent modulation of social behavior, the underlying mechanisms remain unclear. The posterior bed nucleus of the stria terminalis (BST), particularly its principal subdivision (BSTpr), is a critical node regulating pup-directed aggression. Within this region, neurons expressing estrogen receptor 1 (Esr1) promote pup-directed aggression in female mice; however, the specific neuronal subtypes mediating this behavior in males remain unknown. Here, reanalysis of single-cell transcriptomic datasets shows that neurons expressing (+) cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) constitute a subset of Esr1+ neurons within the BST. Exposure to pups selectively increased c-fos expression, a marker of neuronal activation, in BSTpr Cartpt+ neurons in infanticidal virgin males. Chemogenetic activation of these neurons enhanced pup-directed aggression, whereas their ablation suppressed infanticide. Anatomical analyses demonstrated that BSTpr Cartpt+ neurons received direct inhibitory inputs from the anterior commissure nucleus (ACN), a region associated with parental behavior. Additionally, inhibitory transmission from the ACN to BSTpr Cartpt+ neurons was enhanced in fathers. Together, these findings identify BSTpr Cartpt+ neurons as key mediators of pup-directed aggression in male mice, suggesting a neural circuit mechanism underlying the transition from aggression to parental care.

neuroscience↗

bioRxiv2025

Neural Circuit Remodeling Underlying Enhanced Feeding During Pregnancy in Mice

Pregnancy represents a unique physiological state marked by substantial adaptations influencing both behavior and metabolism1. Alterations have been observed across multiple levels--from changes in cellular morphology, synaptic density, and neuroglial interactions to a brain-wide reduction in gray matter volume2-7. While these adaptations are thought to support offspring survival and promote maternal physiological and psychological well-being8, their functional significance remains largely unresolved. In particular, linking localized synaptic plasticity to a broader brain-wide circuit dynamics has posed a major challenge. Using virus-mediated screening in mice, we investigated the pregnancy-induced remodeling of the presynaptic landscape of paraventricular hypothalamic (PVH) oxytocin neurons, a central hub of maternal physiology9,10. Here we show a selective and reversible elimination of excitatory synaptic inputs from the medial preoptic nucleus to PVH oxytocin neurons, displaying region-, cell-type-, and pathway-specificity. This reduction in excitatory drive attenuated the anorexigenic activity of oxytocin neurons during feeding, thereby promoting the increased food intake characteristic of pregnancy. These data demonstrate that the selective suppression of anorexigenic PVH oxytocin neuron activity plays a critical role in appetite regulation during pregnancy. More broadly, our data identify a pregnancy-associated remodeling of hypothalamic neural circuits with direct physiological relevance.

neuroscience↗

bioRxiv2025

Artificially induced torpor during pregnancy impairs fetal growth in mice

Fetal development in endothermic mammals relies on a tightly regulated maternal body temperature. In animal models, deviations from normothermia during gestation cause fetal developmental abnormalities. However, the direct and physiological manipulation of the maternal core temperature has been technologically challenging, as traditional methods involve the imposition of external thermal stress. Recent advances in the identification of thermoregulatory neurons in the mouse preoptic area have allowed precise control of maternal body temperature without altering environmental conditions. Here we show that the activation of excitatory neurons in the medial preoptic area (MPO) induces a torpor-like hypothermic state in pregnant mice. When induced during early gestation, this state resulted in pregnancy loss, likely due to implantation failure. Hypothermia in mid- and late-gestation reduced fetal liver and kidney size and caused severe growth retardation. Similar outcomes were observed following pyroglutamylated RFamide peptide (Qrfp)-expressing neuron activation in the MPO, whereas inhibitory neuron activation had minimal effect. Furthermore, activating MPO excitatory neurons projecting to the dorsomedial hypothalamic nucleus reproduced both the torpor-like state and fetal growth retardation. These results underscore the importance of a stable maternal body temperature in fetal development and establish a new model for studying the effects of altered maternal temperature on embryogenesis.

neuroscience↗

bioRxiv2024

Vasopressin-to-Oxytocin Receptor Crosstalk in the Preoptic Area Underlying Parental Behaviors in Male Mice

The transition to parenthood brings significant changes in behavior toward offspring. For instance, in anticipation of their offspring, male mice shift from infanticidal to caregiving behaviors. While the release of oxytocin from the paraventricular hypothalamus (PVH) plays a critical role in paternal caregiving, it does not fully account for the entire behavioral shift. The specific downstream neurons and signaling mechanisms involved in this process remain obscure. Here, we demonstrate that PVH vasopressin neurons also essentially contribute to a paternal behavioral shift. This vasopressin signal is partially transmitted through oxytocin receptors (OTRs) expressed in the anterior commissure and medial nuclei of the preoptic area. These OTR-expressing neurons receive inputs from both PVH oxytocin and vasopressin neurons and are responsible for expressing paternal caregiving behaviors. Collectively, this non-canonical vasopressin-to-OTR crosstalk within specific limbic circuits acts as a pivotal regulator of paternal behavioral changes in mice. HighlightsO_LIPVH vasopressin neurons are required for and can trigger paternal caregiving behaviors. C_LIO_LIVasopressin-induced paternal behaviors are mediated in part by OTRs in the preoptic area (POA). C_LIO_LIPOA OTR neurons receive inputs from both PVH oxytocin and vasopressin neurons. C_LIO_LIPOA OTR neurons play a critical and facilitative role in promoting paternal caregiving behaviors. C_LI

neuroscience↗

bioRxiv2023

A Prefrontal Neural Circuit for Maternal Behavioural Leaning in Mice

Maternal behaviors, which are crucial for the survival of mammalian infants, require the coordinated operation of multiple brain regions to process infant cues, make decisions, and execute motor plans. Although these processes likely demand higher cognitive functions, the prefrontal areas that regulate limbic parental programs remains poorly understood. Here, we show that the orbitofrontal cortex (OFC) excitatory projection neurons promote alloparental caregiving behaviors in female mice. By chronic microendoscopy, we observed robust yet adaptable representations of pup-directed anticipatory and motor-related activities within the OFC. Some of these plastic responses were significantly overlapped with those related to nonsocial reward signals. The inactivation of OFC output reduced the phasic activities of midbrain dopamine (DA) neurons specifically tied to pup retrieval and impaired the modulation of DA release to the ventral striatum during the acquisition of alloparental behaviors. These findings suggest that the OFC transiently boosts DA activity during the acquisition phase, thereby facilitating the manifestation of alloparental behaviors.

neuroscience↗

bioRxiv2021

Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice

Decades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (OT) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. OT has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of OT signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) of OT or OT receptor (OTR) has little effect on food intake. We herein show that acute conditional KO (cKO) of OT selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of OT rescues the hyperphagic phenotype of the PVH OT cKO model. Furthermore, we show that cKO of OTR selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that OT signaling in the arcuate nucleus suppresses excessive food intake.

neuroscience↗

bioRxiv2021

Plasticity of Neural Connections Underlying Oxytocin-mediated Parental Behaviors of Male Mice

The adult brain can flexibly adapt behaviors to specific life-stage demands. For example, while sexually naive male mice are aggressive to the conspecific young, they start to provide caregiving to infants around the time when their own young are expected. How such behavioral plasticity is implemented at the level of neural connections remains poorly understood. Using viral-genetic approaches, here we establish hypothalamic oxytocin neurons as key regulators of parental caregiving behaviors of male mice. We then used rabies virus-mediated unbiased screen to identify excitatory neural connections originating from the lateral hypothalamus to the oxytocin neurons to be drastically strengthened when male mice become fathers. These connections are functionally relevant, as their activation suppresses pup-directed aggression in virgin males. These results demonstrate the life-stage associated, long-distance, and cell-type-specific plasticity of neural connections in the hypothalamus, the brain region classically assumed to be hard-wired. Highlight- OT is indispensable for parental caregiving behavior of male mice - Activation of OT neurons triggers paternal caregiving behavior in otherwise infanticidal sexually-naive male mice partly via OT ligand - Unbiased rabies virus-mediated screening reveals enhanced connectivity originated from excitatory LHA neurons to OT neurons in fathers. - This structural plasticity can support behavioral plasticity

neuroscience↗