The cochlear hook region detects harmonics beyond the canonical hearing range.

Ultrasound, or sound at frequencies exceeding the conventional range of human hearing, is not only audible to mice, microbats, and dolphins, but also creates an auditory sensation when delivered through bone conduction in humans. Although ultrasound is utilized for brain activation and in hearing aids, the physiological mechanism of ultrasonic hearing remains unknown. In guinea pigs, we found that ultrasound above the hearing range delivered through ossicles of the middle ear evokes an auditory brainstem response and a mechano-electrical transduction current through hair cells, as shown by the local field potential called the cochlear microphonic potential (CM).

Targeting microRNA-145-mediated progressive phenotypes of early bladder cancer in a molecularly defined model.

A progressive subclass of early-stage non-muscle-invasive bladder cancer (NMIBC) frequently recurs and progress into invasive carcinoma, thus decreasing the overall survival rate of NMIBC. However, therapeutic development for progressive NMIBC has been challenging due to the lack of molecularly validated models and agents targeting its genetic vulnerability. We herein molecularly characterized an interventional model of progressive NMIBC and revealed the principal functions and therapeutic potential of microRNA-145 (miR-145) in early bladder tumorigenesis.

Hepatic glycogenolysis and hypometabolism induced by chemogenetic stimulation of C1 neurons.

The precise regulation of blood glucose levels is indispensable for maintaining physiological functions. C1 neurons determine the outflow of the autonomic nervous and endocrine systems to maintain blood glucose levels in the body. In contrast, activation of C1 neurons induces a decrease in activity, suggesting that hypoactivity also participates in maintaining blood glucose levels.

Lunar gravity prevents skeletal muscle atrophy but not myofiber type shift in mice.

Skeletal muscle is sensitive to gravitational alterations. We recently developed a multiple artificial-gravity research system (MARS), which can generate gravity ranging from microgravity to Earth gravity (1 g) in space. Using the MARS, we studied the effects of three different gravitational levels (microgravity, lunar gravity [1/6 g], and 1 g) on the skeletal muscle mass and myofiber constitution in mice.

Repeated activation of C1 neurons in medulla oblongata decreases anti-inflammatory effect via the hypofunction of the adrenal gland adrenergic response.

The immune system is known to be controlled by the autonomic nervous system including sympathetic and parasympathetic (vagus) nerves. C1 neurons in the medulla oblongata, which participate in the control of the autonomic nervous system, are responders to stressors and regulate the immune system. Short-term activation of C1 neurons suppresses inflammation, while the effect of a long-term activation of these neurons on the inflammatory reflex is unclear.

Galvanic vestibular stimulation-induced activation of C1 neurons in medulla oblongata protects against acute lung injury.

Autonomic nerves, including the sympathetic and parasympathetic nerves, control the immune system along with their physiological functions. On the peripheral side, the interaction between the splenic sympathetic nerves and immune cells is important for the anti-inflammatory effects. However, the central mechanism underlying these anti-inflammatory effects remains unclear.

Changes in metabolism and vestibular function depend on gravitational load in mice.

The vestibular system is known to participate in controlling posture and metabolism. Different gravitational environments, including microgravity or hypergravity, cause plastic alteration of the vestibular system, and plasticity is important for adaptation to a novel gravitational environment. However, it is unclear whether the degree of change in vestibular-related physiological function depends on gravitational loading.

Hypergravity load-induced hyperglycemia occurs due to hypothermia and increased plasma corticosterone level in mice.

Hypothermia has been observed during hypergravity load in mice and rats. This response is beneficial for maintaining blood glucose level, although food intake decreases. However, saving glucose is not enough to maintain blood glucose level during hypergravity load.

Polysialylation in a DISC1 Mutant Mouse.

Schizophrenia is a serious psychiatric disorder that affects the social life of patients. Psychiatric disorders are caused by a complex combination of genetic (G) and environmental (E) factors. Polysialylation represents a unique posttranslational modification of a protein, and such changes in neural cell adhesion molecules (NCAMs) have been reported in postmortem brains from patients with psychiatric disorders.

Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury.

Acute kidney injury is highly prevalent and associated with high morbidity and mortality, and there are no approved drugs for its prevention and treatment. Vagus nerve stimulation (VNS) alleviates inflammatory diseases including kidney disease; however, neural circuits involved in VNS-induced tissue protection remain poorly understood. The vagus nerve, a heterogeneous group of neural fibers, innervates numerous organs.

Induced genetic ablation of Rest leads to the alteration of stimulus-induced response of the vagal nerve.

Rest (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells by preventing precocious expression of neuronal genes. In order to further investigate the function of Rest in neurons, we generated and examined mice evoking genetic ablation of Rest specifically in neural tissues by generating Rest conditional knockout mice. As the Rest knockout mice are embryonically lethal, we used a Sox1-Cre allele to excise the floxed Rest gene from the early stage of nerve cell differentiation including neural crest-derived nerve cells.

VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice.

The vestibular system, which is essential for maintaining balance, contributes to the sympathetic response. Although this response is involved in hypergravity load-induced hypothermia in mice, the underlying mechanism remains unknown. This study showed that hypergravity (2g) decreased plasma catecholamines, which resulted in hypoactivity of the interscapular brown adipose tissue (iBAT).

Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment.

The peripheral vestibular organs are sensors for linear acceleration (gravity and head tilt) and rotation. Further, they regulate various body functions, including body stability, ocular movement, autonomic nerve activity, arterial pressure, body temperature, and muscle and bone metabolism. The gravitational environment influences these functions given the highly plastic responsiveness of the vestibular system.

Hypergravity-induced plastic alteration of the vestibulo-sympathetic reflex involves decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex.

The vestibular system contributes to not only eye movement and posture but also the sympathetic response. Plastic alteration of the vestibulo-sympathetic reflex is induced by hypergravity load; however, the mechanism remains unknown. Here, we examined 2 g-induced changing in responsiveness of CAMK2-expressing neurons in the vestibular nucleus complex using optogenetic tools.

Acute stress-induced change in polysialic acid levels mediated by sialidase in mouse brain.

Stress is an important environmental factor influencing human behaviour and causing several mental disorders. Alterations in the structure of polysialic acid (polySia/PSA) due to genetic alterations in ST8SIA2, which encodes a polySia-synthesizing enzyme, are related to certain mental disorders. However, whether stress as an environmental factor leads to changes in polySia structure is unknown.

Non-canonical cholinergic anti-inflammatory pathway-mediated activation of peritoneal macrophages induces Hes1 and blocks ischemia/reperfusion injury in the kidney.

The cholinergic anti-inflammatory pathway (CAP) links the nervous and immune systems and modulates innate and adaptive immunity. Activation of the CAP by vagus nerve stimulation exerts protective effects in a wide variety of clinical disorders including rheumatoid arthritis and Crohn's disease, and in murine models of acute kidney injury including ischemia/reperfusion injury (IRI). The canonical CAP pathway involves activation of splenic alpha7-nicotinic acetylcholine receptor (α7nAChR)-positive macrophages by splenic β2-adrenergic receptor-positive CD4+ T cells.

FGF2-responsive genes in human dental pulp cells assessed using a rat spinal cord injury model.

The central nervous system in adult mammals does not heal spontaneously after spinal cord injury (SCI). However, SCI treatment has been improved recently following the development of cell transplantation therapy. We recently reported that fibroblast growth factor (FGF) 2-pretreated human dental pulp cells (hDPCs) can improve recovery in a rat model of SCI.

Effects of hypergravity on the gene expression of the hypothalamic feeding-related neuropeptides in mice via vestibular inputs.

The effects of hypergravity on the gene expression of the hypothalamic feeding-related neuropeptides in sham-operated (Sham) and vestibular-lesioned (VL) mice were examined by in situ hybridization histochemistry. Corticotrophin-releasing hormone (CRH) in the paraventricular nucleus was increased significantly in Sham but not in VL mice after 3 days of exposure to a 2 g environment compared with a 1 g environment. Significant decreases in pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript and significant increases in neuropeptide Y, agouti-related protein in the arcuate nucleus and orexin in the lateral hypothalamic area were observed in both Sham and VL mice.

Role of C1 neurons in anti-inflammatory reflex: Mediation between afferents and efferents.

Neuroimmune communication, the connection between the autonomic regulatory pathway and immune cells, has been implicated in the regulation of immune function and inflammation. The role of afferents (vagal afferent and somatic sensory nerves) and efferents (autonomic nervous and hypothalamic-pituitary-adrenal systems) in the inflammatory reflex has been well studied; however, the central pathway remains unknown. C1 neurons include both catecholaminergic and glutamatergic neurons, which are located in the rostral ventrolateral medulla.

Comparison among ultrasonic, electrical apparatus, and toxic chemicals for vestibular lesion in mice.

Background: The vestibular lesion (VL) is required to examine the physiological function of the vestibular system in animals. Toxic chemicals or electrical apparatus have been used for the VL, however, they are not ideal as they have low specificity, and can result in unintended damage, and systemic toxic effect.

New Method: Localized vibration-induced VL, using an ultrasonicator, is expected to overcome the problems associated with chemical and electrical lesions.

Chlorpromazine Increases the Expression of Polysialic Acid (PolySia) in Human Neuroblastoma Cells and Mouse Prefrontal Cortex.

The neural cell adhesion molecule (NCAM) is modified by polysialic acid (polySia or PSA) in embryonic brains. In adult brains, polySia modification of NCAM is only observed in restricted areas where neural plasticity, remodeling of neural connections, or neural generation is ongoing although the amount of NCAM remains unchanged. Impairments of the polySia-expression and several single nucleotide polymorphisms (SNPs) of the polysialyltransferase (polyST) ST8SIA2 gene are reported to be associated with schizophrenia and bipolar disorder.

Blood Pressure Regulation by the Rostral Ventrolateral Medulla in Conscious Rats: Effects of Hypoxia, Hypercapnia, Baroreceptor Denervation, and Anesthesia.

Current understanding of the contribution of C1 neurons to blood pressure (BP) regulation derives predominantly from experiments performed in anesthetized animals or reduced preparations. Here, we use ArchaerhodopsinT3.0 (ArchT) loss-of-function optogenetics to explore BP regulation by C1 neurons in intact, unanesthetized rats.

C1 neurons mediate a stress-induced anti-inflammatory reflex in mice.

C1 neurons, located in the medulla oblongata, mediate adaptive autonomic responses to physical stressors (for example, hypotension, hemorrhage and presence of lipopolysaccharides). We describe here a powerful anti-inflammatory effect of restraint stress, mediated by C1 neurons: protection against renal ischemia-reperfusion injury. Restraint stress or optogenetic C1 neuron (C1) stimulation (10 min) protected mice from ischemia-reperfusion injury (IRI).