Biology subjects

Minami, M.

Publications and source records attributed to Minami, M..

9 recordsLinked to original sources

bioRxiv2026

Rabies virus antagonizes interferon signaling by targeting phosphorylated STAT1 tetramers

AO_SCPLOWBSTRACTC_SCPLOWRabies virus phosphoprotein (P protein) antagonizes interferon signalling by selectively targeting activated STAT1 protein, but the structural basis for the selective recognition of activated STAT1 has remained unclear. Here we report cryo-EM structures of tyrosine-phosphorylated STAT1 (pY-STAT1) in complex with the C-terminal domain of P protein (P-CTD). P-CTD engages the pY-STAT1 tetramer through three discrete interfaces, contacting two DNA-binding domains within a pY-mediated STAT1 dimer and the N-terminal domain of a third STAT1 protomer. This binding mode explains how P-CTD selectively recognizes activated STAT1, occludes surfaces required for importin 5 and DNA binding, and stabilizes the compact tetrameric state, thereby restricting the conformational transition required for cooperative DNA binding. Cell-based assays further indicate that distinct P-CTD surfaces differentially contribute to antagonism of type I and type II interferon signalling. Further, by acting as an anchoring molecule, P-CTD also enabled structural elucidation of the complete STAT1 structures in the tetramer. Together, these data reveal critical mechanisms in viral immune evasion and pathogenesis, and fundamental innate immune signaling.

molecular biology↗

bioRxiv2026

Oxytocin regulates TN-GnRH3 circuit maturation and mate preference through C1q-dependent synaptic mechanisms

Oxytocin is a key regulator of social behavior, yet how it shapes the neural circuits underlying these behaviors remains unclear. Here, we show that oxytocin signaling is required for the proper maturation of terminal nerve gonadotropin-releasing hormone 3 (TN-GnRH3) circuits that regulate female mate preference in medaka. Disruption of oxytocin signaling reduced expression of the complement component C1q, altered microglial properties, and increased TN-GnRH3 innervation in the optic tectum and dorsolateral telencephalon, suggesting impaired synaptic refinement. In addition, TN-GnRH3 neurons in mutants exhibited disrupted clustering and failed to increase firing frequency in response to visual stimulation, indicating functional deficits. Furthermore, c1qb mutants phenocopied the behavioral and neuronal abnormalities observed in oxytocin signaling-deficient mutants. Together, our findings suggest that oxytocin signaling links microglia-associated synaptic refinement to neural circuit maturation, thereby revealing a previously unrecognized role for oxytocin in shaping social behavior.

neuroscience↗

bioRxiv2025

Closed-loop heart rate regulation based on medulla stimulation

Cardiovasular diseases are often accompanied with the dysfunctions of autonomic nervous system. Cardiac neuromodulation including vagus nerve stimulation have emerged as alternative therapies by restoring sympatho-vagal balance. In this work, a medulla stimulation strategy was developed to precisely regulate the heart rate. The stimulation parameters effecting on cardiac function were assessed in open-loop experiments. The cardiac effects of rostral and caudal medulla stimulation were enhanced with increased stimulus frequency. We further investigated whether medulla stimulation can temporarily regulate the heart rate at predetermined levels using on-off closed-loop control. Additionally, we tested the capacity of medullary stimulation to rebalance autonomic function under peripheral imbalance conditions caused by dobutamine and neostigmine administration. The performance of heart rate regulation was quantified by the control degree and root mean squared error. The results demonstrate the feasibility of medulla stimulation for regulating sympathetic activity, emphasizing its potential therapeutic use in cardiac disorders.

physiology↗

bioRxiv2025

Infraslow histaminergic dynamics govern priming states to gate moment-to-moment memory accessibility

Memory expression fluctuates even in response to identical cues, suggesting that ongoing brain states bias memory accessibility. However, the cellular and circuit principles governing these state-dependent fluctuations remain unclear. Here, we show that spontaneous pre-cue activity of histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) modulates the expression of reward-associative memory in mice. TMN histaminergic activity exhibited infraslow dynamics (0.05-0.1 Hz) that closely tracked an integrated brain-body state. Closed-loop cue delivery during high histaminergic states enhanced memory expression. Brief optogenetic activation or inhibition of these neurons before the cue bidirectionally modulated memory expression, and direct activation of histaminergic terminals in the basolateral amygdala (BLA) was sufficient to enhance memory expression. Furthermore, histaminergic inhibition before the cue impaired the cue-evoked BLA population response. Thus, ongoing histaminergic activity exerts an infraslow, state-setting influence that primes BLA circuits for robust cue responses, and in turn, modulates moment-to-moment memory accessibility.

neuroscience↗

bioRxiv2025

Competing valence-related roles of dopamine in the tail of the striatum

Understanding how the brain evaluates aversion and appetition to guide behavior remains an open question. Here, we investigated the role of dopamine signaling in the tail of the striatum (TS) in regulating competing valence-based behaviors and learning. TS dopamine dynamics were monitored as mice performed a classical conditioning task in which an odor cue predicted either an aversive air puff or a water reward. Initially, mice exhibited anticipatory blinking, which diminished over time, while anticipatory licking emerged later, coinciding with adaptation to the air puff. Dopamine responses in the TS to the air puff and its associated odor were initially elevated but declined with repeated exposure. Optogenetic disruption of this decline suppressed adaptation and hindered appetitive learning. These findings demonstrate that TS dopamine dynamics are essential for behavioral adaptation to aversive stimuli, which indirectly facilitates appetitive learning, underscoring a regulatory mechanism for shifting between defensive and reward-seeking behaviors.

neuroscience↗

bioRxiv2025

Chronic social defeat causes dysregulation of systemic glucose metabolism via the cerebellar fastigial nucleus

Chronic psychological stress leads to hyperglycemia through the endocrine and sympathetic nervous systems, which contributes to the development of type II diabetes mellitus (T2DM). Higher plasma corticosteroids after stress is one well-established driver of insulin resistance in peripheral tissues. However, previous studies have indicated that only a fraction of patients with depression and post-traumatic disorder (PTSD) who develop T2DM exhibit hypocortisolism, so corticosteroids do not fully explain psychological stress-induced T2DM. Here, we find that chronic social defeat stress (CSDS) in mice enhances gluconeogenesis, which is accompanied by a decrease in plasma insulin, an increase in plasma catecholamines, and a drop in plasma corticosterone levels. We further reveal that these metabolic and endocrinological changes are mediated by the activation of neurons projecting from the cerebellar fastigial nucleus (FN) to the medullary parasolitary nucleus (PSol). These neurons are crucial in shifting the bodys primary energy source from glucose to lipids. Additionally, data from patients with depression reveal correlations between the presence of cerebellar abnormalities and both worsening depressive symptoms and elevated HbA1c levels. These findings highlight a previously unappreciated role of the cerebellum in metabolic regulation and its importance as a potential therapeutic target in depression, PTSD, and similar psychological disorders.

neuroscience↗

bioRxiv2024

Identification of Large Japanese field mouse Apodemus speciosus food plant resources in an industrial green space using DNA metabarcoding

DNA metabarcoding was employed to identify the food plant resources of the Large Japanese field mouse Apodemus speciosus, inhabiting an artificial green space on reclaimed land on the Chita Peninsula in Aichi Prefecture, Central Japan, from 2012 to 2014. DNA metabarcoding was performed using high-throughput sequencing of partial rbcL sequences extracted from feces samples collected in the study area. The obtained sequences, which were analyzed using a constructed local database, revealed that a total of 72 plant taxa were utilized as food plant resources by A. speciosus. Of these plant taxa, 43 could be assigned to species (59.7%), 16 to genus (22.2%), and 13 to family (18.1%). Of the 72 plant taxa identified in this study, the dominant families throughout all collection periods were Lauraceae (81.0% of 100 fecal samples), followed by Fagaceae (70.0%), Rosaceae (68.0%), and Oleaceae (48.0%). Fifty of the 72 plant taxa identified as food plant resources were woody plants. An analysis employing rarefaction techniques for each season in the study site indicated comprehensive coverage of the food plant resources, ranging from 86.4% in winter to 93.6% in spring. Further, 96.5% of the food plant taxa were found throughout the study period. The findings showed that DNA metabarcoding using a local database constructed from the National Center for Biotechnology Information (NCBI) database and field surveys was effective for identifying the dominant food plants in the diet of A. speciosus. The results of this study provided basic information that can be applied to formulation and implementation of management and conservation strategies for local wildlife.

molecular biology↗

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↗

bioRxiv2021

Identification of Lagopus muta japonica plant food resources in the Northern Japan Alps using DNA metabarcoding

DNA metabarcoding was employed to identify plant-derived food resources of the Japanese rock ptarmigan (Lagopus muta japonica), registered as a natural living monument in Japan, in the Northern Japanese Alps in Toyama Prefecture, Japan, in July to October, 2015-2018. By combined use of rbcL and ITS2 local databases of 74 alpine plant species found in the study area, a total of 43 plant taxa were identified and could be assigned to 40 species (93.0%), two genera (4.7%), and one family (2.3%). Rarefaction analysis of each sample collection period showed that this study covered more than 90% of the plant food resources found in the study area. Of the 21 plant families identified using the combined rbcL and ITS2 local databases, the most dominant families were Ericaceae (98.1% of 105 fecal samples), followed by Rosaceae (42.9%), Apiaceae (35.2%), and Poaceae (19.0%). In all fecal samples examined, the most frequently encountered plant species were Vaccinium ovalifolium var. ovalifolium (69.5%), followed by Empetrum nigrum var. japonicum (68.6%), Vaccinium sp. (54.3%), Kalmia procumbens (42.9%), and Tilingia ajanensis (34.3%). Rarefaction analysis of each collection period in the study revealed that this study covered more than 90% (from 91.0% in July to 97.5% in September) of the plant food resources found in the study area, and 98.1% of the plant food taxa were covered throughout the entire study period. Thus, DNA metabarcoding using the rbcL and ITS2 local databases of alpine plants in combination and rarefaction analysis are considered to be well suited for estimating the dominant food plants in the diet of Japanese rock ptarmigans. Further, the local database constructed in this study can be used to survey other areas with similar flora.

ecology↗