Biology subjects

Sasaoka, T.

Publications and source records attributed to Sasaoka, T..

8 recordsLinked to original sources

bioRxiv2026

Time-restricted feeding corrects aggravation of glucose intolerance and circadian disruption induced by weight cycling in obese young mice

Weight cycling (WC), defined as weight gain, loss, and regain, is common in obesity, but its metabolic consequences remain unclear. We tested whether WC-aggravated glucose intolerance in obesity is age-dependent and linked to circadian disruption. Young (7w) and mid-aged (12m) mice underwent a 15-week dietary intervention: Lean and Obese mice fed normal chow (NC) and high-fat diet (HFD) throughout, respectively. WC mice undergone HFD-induced weight gain, NC-induced weight loss, and a second HFD-induced weight regain. Late-onset obese (LO) mice ate HFD only paralleling weight regain of WC. In young, but not mid-aged mice, prior obesity accelerated weight regain upon HFD re-exposure, and aggravated glucose intolerance beyond that observed in Obese mice. This occurred without a worse adipose inflammatory profile. Rather, WC young mice exhibited blunting of light/dark-phase oscillation of feeding and energy metabolism, adipose and hepatic core clock gene oscillation, and increased hepatic expression of clock and gluconeogenic genes during the inactive phase. Restricting food availability to the active phase did not alter final weight regain, but improved glucose tolerance selectively in WC mice, normalized hepatic gluconeogenic and clock-genes expression in both liver and adipose tissue. These findings identify circadian disruption as a modifiable mediator of the adverse metabolic impact of WC in young-adulthood obesity. HighlightsO_LIWeight cycling is common in obesity, but whether it worsens metabolic dysfunction beyond persistent obesity remains unclear. C_LIO_LIWe asked whether weight cycling aggravates glucose intolerance in an age-dependent manner and whether circadian disruption contributes to this effect. C_LIO_LIIn young, but not mid-aged mice, weight cycling accelerated weight regain and worsened glucose intolerance, accompanied by blunted diurnal oscillation of behavioral parameters and core clock gene expression, without exaggerated adipose inflammation. C_LIO_LIActive-phase time-restricted feeding improved WC-induced aggravated glucose tolerance and circadian oscillation, identifying circadian disruption as a modifiable mechanism linking weight cycling adverse metabolic outcomes in young-adulthood obesity. C_LI

biochemistry↗

bioRxiv2026

A Knock-In Igfn1iCre transgenic mouse line provides partial developmental access to type-7 bipolar cells

1.Functional neuronal circuits in the vertebrate retina emerge through coordinated developmental events, yet the timeline by which bipolar cells acquire visual feature selectivity remains unclear. A major barrier is the limited genetic access to bipolar subtypes during early postnatal stages. Recent comprehensive transcriptomic study points to Igfn1 as a molecular marker for type-7 bipolar cells (BC 7), a subtype that exhibits direction-selective glutamate releases in adult. Here, we generated an Igfn1iCre knock-in mouse line and characterized Igfn1-positive cell morphology from postnatal day 4(P4) to adult using Cre-dependent tdTomato reporter mice. We found Igfn1-positive cells in the inner retina by P12-P15, predominantly labelling bipolar cells and some amacrine populations. At P15, about 71% of labelled bipolar cells stratified their axons in the S4 sublamina of the inner plexiform layer, consistent with BC 7 morphology. In adult retina, the widespread Igfn1-labelling appears slightly dominated in amacrine cells. To validate these observations, we analysed Igfn1 expression in the Mouse Retina Cell Atlas and confirmed strong Igfn1 enrichment in BC 7 and expression in additional retinal cell types, mirroring experimental results. Overall, these results reveal Igfn1iCre as a potential developmental tool for BC 7 access in the retina.

neuroscience↗

bioRxiv2023

The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body.

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of integration of intero-exteroceptive information to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of our self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0{degrees}, 90{degrees}, and 270{degrees} relative to the upright orientation, and when the front view presented as compared to the back view. Corresponding to the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC). Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants interoceptive sensitivity, as assessed through the heartbeat detection task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues for the purpose of spatially transforming the image of our self-body.

neuroscience↗

bioRxiv2021

Neurexins in serotonergic neurons regulate serotonin transmission and complex mouse behaviors

Extensive serotonin (5-HT) innervation throughout the brain corroborates 5-HTs modulatory role in numerous cognitive activities. Volume transmission is the major mode for 5-HT transmission but mechanisms underlying 5-HT signaling are still largely unknown. Abnormal brain 5-HT levels and function have been implicated in autism spectrum disorder (ASD). Neurexin (Nrxn) genes encode presynaptic cell adhesion molecules important for the regulation of synaptic neurotransmitter release, notably glutamatergic and GABAergic transmission. Mutations in Nrxn genes are associated with neurodevelopmental disorders including ASD. However, the role of Nrxn genes in the 5-HT system is poorly understood. Here, we generated a mouse model with all three Nrxn genes disrupted specifically in 5-HT neurons to study how Nrxns affect 5-HT transmission. Loss of Nrxns in 5-HT neurons reduced the number of serotonin neurons in the early postnatal stage, impaired 5-HT release, and decreased 5-HT release sites and serotonin transporter expression. Furthermore, 5-HT neuron-specific Nrxn knockout reduced sociability and increased depressive-like behavior. Our results highlight functional roles for Nrxns in 5-HT neurotransmission, 5-HT neuron survival, and the execution of complex behaviors.

neuroscience↗

bioRxiv2021

Interoceptive sensitivity modulates heart rate and insula activity when listening to music

Interoception plays an important role in emotion processing, but the relationship between the physiological responses associated with emotional experience and interoception is unclear. In this study, we measured interoceptive sensitivity using the heartbeat discrimination task and investigated the effects of individual differences in interoceptive sensitivity on changes in heart rate and insula activity in response to music-induced emotions. We found that the heart rate increased when listening to the music pieces rated as emotionally high-touching in the high interoceptive sensitivity group only. Compared to the emotionally low-touching music, listening to the emotionally high-touching music was associated with higher insula activity. Furthermore, relative to individuals with low interoceptive sensitivity, the region of interest analysis of the insula subregions for individuals with high interoceptive sensitivity revealed significant activity in the bilateral dorsal granular insula, the right ventral dysgranular insula, and the right granular and dorsal dysgranular insula while listening to the high-touching music pieces. Our results suggest that individuals with high interoceptive sensitivity use their physical condition to assess their emotional level when listening to music. Furthermore, the insula activity may reflect the use of interoception to estimate emotions.

neuroscience↗

bioRxiv2021

Neural basis for anxiety and anxiety-related physiological responses during simulated driving: An fMRI study

While the exteroceptive and interoceptive prediction of a negative event increases a persons anxiety in daily life situations, the relationship between the brain mechanism of anxiety and the anxiety-related autonomic response has not been fully understood. In this fMRI study, we examined the neural basis of anxiety and anxiety-related autonomic responses in a daily driving situation. Participants viewed a driving video clip in the first-person perspective. During the video clip, participants were presented with a cue to indicate whether a subsequent crash could occur (attention condition) or not (safe condition). Enhanced activities in the anterior insula, bed nucleus of the stria terminalis, thalamus, and periaqueductal gray, and higher sympathetic nerve responses (pupil dilation and peripheral arterial stiffness) were triggered by the attention condition but not with the safe condition. Autonomic response-related functional connectivity was detected in the visual cortex, cerebellum, brainstem, and MCC/PCC with the right anterior insula and its adjacent regions as seed regions. Thus, the right anterior insula and adjacent regions, in collaboration with other regions play a role in eliciting anxiety based on the prediction of negative events, by mediating anxiety-related autonomic responses according to interoceptive information.

neuroscience↗

bioRxiv2020

A Specific Neuroligin3-αNeurexin1 Code Regulates GABAergic Synaptic Function in Mouse Hippocampus

Synapse formation and regulation require interactions between pre- and postsynaptic proteins, notably cell adhesion molecules (CAMs). It has been proposed that the functions of neuroligins (Nlgns), postsynaptic CAMs, rely on the formation of trans-synaptic complexes with neurexins (Nrxns), presynaptic CAMs. Nlgn3 is a unique Nlgn isoform that localizes at both excitatory and inhibitory synapses. However, Nlgn3 function mediated via Nrxn interactions is unknown. Here, we demonstrate that Nlgn3 localizes at postsynaptic sites apposing vesicular glutamate transporter 3-expressing (VGT3+) inhibitory terminals and regulates VGT3+ inhibitory interneuron-mediated synaptic transmission in mouse organotypic slice cultures. Gene expression analysis of interneurons revealed that the Nrxn1+AS4 splice isoform is highly expressed in VGT3+ interneurons as compared with other interneurons. Most importantly, postsynaptic Nlgn3 requires presynaptic Nrxn1+AS4 expressed in VGT3+ interneurons to regulate inhibitory synaptic transmission. Our results indicate that specific Nlgn-Nrxn interactions generate distinct functional properties at synapses.

neuroscience↗

bioRxiv2019

Quantification of anticipation of excitement with three-axial model of emotion with EEG

ObjectivesMultiple facets of human emotions underlie diverse and sparse neural mechanisms. Amongst many models of emotions, the circumplex model of emotion is one of a significant theory. The use of the circumplex model allows us to model variable aspects of emotion; however, such momentary expression of ones internal mental state still lacks to consider another, the third dimension of time. Here, we report an exploratory attempt to build a three-axial model of human emotion to model our sense of anticipatory excitement, "Waku-Waku (in Japanese)," when people are predictively coding upcoming emotional events. ApproachElectroencephalography (EEG) was recorded from 28 young adult participants while they mentalized upcoming emotional pictures. Three auditory tones were used as indicative cues, predicting the likelihood of valence of an upcoming picture, either positive, negative, or unknown. While seeing an image, participants judged its emotional valence during the task, and subsequently rated their subjective experiences on valence, arousal, expectation, and Waku-Waku immediately after the experiment. The collected EEG data were then analyzed to identify contributory neural signatures for each of the three axes. Main ResultsA three axial model was built to quantify Waku-Waku. As was expected, this model revealed considerable contribution of the third dimension over the classical two-dimension model. Distinctive EEG components were identified. Furthermore, a novel brain-emotion interface is proposed and validated within the scope of limitations. SignificanceThe proposed notion may shed new light on the theories of emotion and supports multiplex dimensions of emotion. With an introduction of the cognitive domain for a brain-computer-interface, we propose a novel brain-emotion-interface. Limitations and potential applications are discussed.

neuroscience↗