Spectral Mismatch Effect of Ultraviolet Radiometers in Actual UV-C Measurement.

The management of radiant exposure to ultraviolet (UV) radiation, especially in the wavelength range from 100 nm to 280 nm (i.e. UV-C), is important for virus inactivation or photobiological safety. Recently, many commercial UV radiometers have been used to measure UV-C irradiance for industrial and public applications. The accuracy of the four types of commercial UV radiometers was investigated by comparing the reference irradiance values obtained from the spectral irradiance standard. It was found that the displayed values of the UV radiometers have discrepancies, such that the measured value can be more than twice the actual value in a certain case. The spectral mismatch between the calibration and test sources is a major factor in the discrepancies in the UV-C measurements. With spectral mismatch correction, most corrected values show a tendency to improve the result to approaching the reference values within 20%. Users need to provide spectral information about the source and radiometer used for UV-C measurement.

Histograms of Frequency-Intensity Distribution Deep Learning to Predict the Seizure Liability of Drugs in Electroencephalography.

Detection of seizures as well as that of seizure auras is effective in improving the predictive accuracy of seizure liability of drugs. Whereas electroencephalography has been known to be effective for the detection of seizure liability, no established methods are available for the detection of seizure auras. We developed a method for detecting seizure auras through machine learning using frequency-characteristic images of electroencephalograms. Histograms of frequency-intensity distribution prepared from electroencephalograms of rats analyzed during seizures induced with 4-aminopyridine (6 mg/kg), strychnine (3 mg/kg), and pilocarpine (400 mg/kg), were used to create an artificial intelligence (AI) system that learned the features of frequency-characteristic images during seizures. The AI system detected seizure states learned in advance with 100% accuracy induced even by convulsants acting through different mechanisms, and the risk of seizure before a seizure was detected in general observation. The developed AI system determined that the unlearned convulsant Tramadol (150 mg/kg) was the risk of seizure and the negative compounds aspirin and vehicle were negative. Moreover, the AI system detected seizure liability even in electroencephalography data associated with the use of 4-aminopyridine (3 mg/kg), strychnine (1 mg/kg), and pilocarpine (150 mg/kg), which did not induce seizures detectable in general observation. These results suggest that the AI system developed herein is an effective means for electroencephalographic detection of seizure auras, raising expectations for its practical use as a new analytical method that allows for the sensitive detection of seizure liability of drugs that has been overlooked previously in preclinical studies.

Serotonin 5-HT4 Receptor Agonists Improve Facilitation of Contextual Fear Extinction in an MPTP-Induced Mouse Model of Parkinson's Disease.

Previously, we found that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) model mice (PD mice) showed facilitation of hippocampal memory extinction via reduced cyclic adenosine monophosphate (cAMP)/cAMP-dependent response element-binding protein (CREB) signaling, which may cause cognitive impairment in PD. Serotonergic neurons in the median raphe nucleus (MnRN) project to the hippocampus, and functional abnormalities have been reported. In the present study, we investigated the effects of the serotonin 5-HT4 receptor (5-HT4R) agonists prucalopride and velusetrag on the facilitation of memory extinction observed in PD mice. Both 5-HT4R agonists restored facilitation of contextual fear extinction in PD mice by stimulating the cAMP/CREB pathway in the dentate gyrus of the hippocampus. A retrograde fluorogold-tracer study showed that γ-aminobutyric acid-ergic (GABAergic) neurons in the reticular part of the substantia nigra (SNr), but not dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc), projected to serotonergic neurons in the MnRN, which are known to project their nerve terminals to the hippocampus. It is possible that the degeneration of the SNpc DAergic neurons in PD mice affects the SNr GABAergic neurons, and thereafter, the serotonergic neurons in the MnRN, resulting in hippocampal dysfunction. These findings suggest that 5HT4R agonists could be potentially useful as therapeutic drugs for treating cognitive deficits in PD.

Supralinear behavior and its wavelength dependence of silicon photodiodes with over-filled illumination in visible range.

Spectral supralinear behavior of silicon (Si) photodiodes (PDs) with over-filled illumination in the visible region was investigated. Comparing the results with the supralinearity results in under-filled illumination conditions, the supralinearities of the Si PDs with over-filled illumination sharply increased at the photocurrent over hundreds of nA, and the maximum supralinearity value of approximately 5% was observed at the 405-nm wavelength. To validate the supralinearity increase under over-filled illumination in visible light, the linearity factor and the photocurrent relating to the Si PD position and their wavelength dependence were examined. The linearity factors increased as the laser beam approached the Si PD electrode as well as with decreasing wavelength, although the examined photocurrent decreased as the laser beam strayed off the beam detection area of the Si PD. These results show that the supralinearity with over-filled illumination in the visible region was caused by the recombination losses near the Si PD electrode. These experimental results can help obtain accurate measurements with photometry instruments constructed of Si PDs and for the three-dimensional theoretical modeling of the Si photo devices.

Rolipram improves facilitation of contextual fear extinction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease.

Cognitive impairment often occurs in Parkinson's disease (PD), but the mechanism of onset remains unknown. Recently, we reported that PD model mice produced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) show facilitation of hippocampal memory extinction, which may be the cause of cognitive impairment in PD. When we examined the cAMP/CREB signaling in the hippocampus, decreased levels of cAMP and phosphorylated CREB were observed in the dentate gyrus (DG) of MPTP-treated mice. Administration of rolipram improved the memory deficits with concomitant recovery of cAMP and phosphorylated CREB levels, suggesting that reduced cAMP/CREB signaling in the DG leads to cognitive impairment in MPTP-treated mice.

The effects of unilateral lesion of the tuberomammillary nucleus E2 sub-region on nocturnal feeding and related behaviors in mice.

AIMS: Bilateral lesions of the mesencephalic trigeminal sensory nucleus (Me5), which receives histaminergic neurons from the tuberomammillary nucleus (TMN), alter nocturnal feeding and related behaviors in mice, concomitant with a decrease in orexin mRNA level in the perifornical area (PFA) during the dark phase. Therefore, we investigated the neuronal input to the TMN from the Me5, as well as the effects of TMN lesions on the circadian profiles of feeding and related behaviors. MAIN METHODS: We examined the presence of neurons projecting from the Me5 to the TMN by direct injection of a retrograde tracer, Fluorogold, into the TMN E2 sub-region (TMN-E2). We also assessed feeding, drinking, and locomotion for 24h using an automated feeding behavior measurement apparatus, and analyzed the hypothalamic orexin mRNA levels in both TMN-lesion and sham-operated mice. KEY FINDINGS: The presence of neuronal projections from the Me5 to the TMN-E2 was confirmed. A decrease in food and water intake and locomotion during the latter half of the dark phase was delayed in TMN-lesion but not sham-operation mice. Further, orexin mRNA expression levels were higher in both the PFA and lateral hypothalamus area (LHA) in TMN-E2-lesion mice relative to control mice, during the early half of the dark phase compared with the light phase. SIGNIFICANCE: Our results suggest that histaminergic neurons in the TMN-E2 receive signals from the Me5 that modulate a switch from dark to light phase feeding and related behaviors, which in turn may be regulated by orexin neurons in the PFA and/or LHA.

Serotonin modulates the dehydration-induced changes in tolerance for bitter water.

Drinking behavior is regulated by endogenous factors such as the hydration condition of animals and exogenous factors such as the taste of ingested fluids. These factors have been suggested to interact with each other via serotonergic (5-HT) signaling to regulate drinking behavior. In the present study, we examined how dehydration affects the intake of bitter water, which suppresses drinking behavior, via 5-HT signaling. Water deprivation increased water intake for 1h, depending on the duration of water deprivation. The intake of 1mM quinine, which is a bitter tastant, was lower than that of water in mice deprived of water for 24h but not 48 h. We next examined the involvement of the dorsal raphe nucleus (DRN) and median raphe nucleus (MRN), which contain a large population of 5-HT neurons, in changing tolerance for quinine intake after water deprivation. The intake of quinine following water deprivation for 24h, but not 48 h, increased the number of tryptophan hydroxylase-positive neurons expressing c-Fos in the DRN, but not in the MRN. Moreover, administration of paroxetine, a selective serotonin reuptake inhibitor, decreased the intake of quinine solution, but not water, in mice deprived of water for 48 h, indicating that paroxetine treatment restored the aversion to quinine. These results suggest that unresponsiveness of 5-HT neurons in the DRN may be involved in the dehydration-induced increase in tolerance for bitter water.

Selective loss of dopaminergic neurons in the substantia nigra pars compacta after systemic administration of MPTP facilitates extinction learning.

AIMS: Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). In PD, thinking and retrieval deficits often arise from cognitive impairments. However, the mechanism of cognitive disorders in PD remains unknown. Therefore, we investigated cognitive function in PD model mice produced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which specifically destroys the DAergic neurons in the SNpc. MAIN METHODS: We evaluated the cognitive function of MPTP-treated mice (PD mice) using the contextual fear conditioning test. In the test, each experiment consists of three phases: training, re-exposure, and testing. Mice were trained with a foot shock (a weak unconditioned stimulus: 1mA/2s duration, once, or an intense unconditioned stimulus: 2mA/2s duration, twice), and 24h later, mice were re-exposed to the training context for 3min to determine reconsolidation or 30min to determine extinction. The percentage of time spent freezing was measured during the test session as indexes of memory consolidation, reconsolidation, and extinction. KEY FINDINGS: Reconsolidation of PD mice occurred normally but memory extinction was facilitated in PD mice compared to control mice. Moreover, memory retention in PD mice was attenuated earlier than in controls following repeated conditioned stimuli every day. SIGNIFICANCE: PD mice with selective loss of DAergic neurons in the SNpc showed attenuated memory retention, probably via facilitated extinction learning.

Comparison of c-Fos expression in brain regions involved in maternal behavior of virgin and lactating female mice.

Maternal care is indispensable for the survival of mammalian offspring. Although virgin female mice avoid pups, they actively display maternal behavior after parturition. To determine which brain regions are involved in the qualitative differences observed in the responses of virgin and lactating females to pups, we compared the expression of c-Fos, which is a marker of neuronal activation, in brain regions involved in regulating maternal behavior. Pup presentation increased the number of c-Fos-positive cells in both the ventrotegmental area (VTA) and nucleus accumbens to a greater extent in lactating females than in virgin females. The bed nucleus of striaterminalis (BNST), which innervates VTA neurons to regulate both aversive and rewarding responses, showed increased number of c-Fos-positive cells following pup presentation in virgin females, butnotin lactating females. On the other hand, the number of c-Fos-positive cells in the medial preoptic area (MPOA) increased in both virgin and lactating females. The number of c-Fos-positive cells in lactating females not presented with pups was high and similar to that in virgin females presented with pups. Moreover, c-Fos-positive GABAergicneurons projecting from the MPOA to the BNST was confirmed using a retrograde tracer Fluorogold in lactating females. Our results indicate that constitutive GABAergic modulation projecting from the MPOA may suppress the activity of BNST neurons and prevent avoidance responses to pups in lactating females.

The effects of bilateral lesions of the mesencephalic trigeminal sensory nucleus on nocturnal feeding and related behaviors in mice.

AIMS: The mesencephalic trigeminal sensory nucleus (Me5), which receives signals originating from oral proprioceptors and projects its fibers to the hypothalamus, regulates mastication and modulates satiation. Because the Me5 neurons display circadian rhythms in circadian mPer1 gene expression and bilateral Me5 lesions change feeding and exploratory behavior profiles, we speculated that Me5 may influence the daily timing of feeding. Therefore, we explored the effects of bilateral caudal Me5 lesions on the circadian profiles of feeding and its related behaviors. MAIN METHODS: We measured the activities of feeding, drinking, and locomotion for 24h using an automated feeding behavior measurement apparatus and analyzed the mRNA expression levels of hypothalamic orexigenic and anorexigenic signaling molecules in both Me5-lesioned and sham-operated mice. KEY FINDINGS: Food and water intake and locomotor activity decreased significantly in Me5-lesioned mice during the dark phase without affecting these total indexes when measured over the entire day. Analysis of the mRNA expression levels of hypothalamic orexigenic and anorexigenic signaling molecules showed that prepro-orexin (orexin) mRNA in the perifornical area was significantly decreased during the dark phase only in Me5-lesioned mice. SIGNIFICANCE: Bilateral caudal Me5 lesions alter the nocturnal properties of food and water intake and locomotor activity in mice and decrease the mRNA expression level of orexin in the perifornical area during the dark phase. These results suggest that Me5 activity may influence the nocturnal properties of feeding and its related behaviors by adjusting the activity of orexin neurons in the perifornical area.

Post-weaning mice fed exclusively milk have deficits in induction of long-term depression in the CA1 hippocampal region and spatial learning and memory.

Previously, we have found that post-weaning mice fed exclusively milk display low-frequency exploratory behavior compared to mice fed a food pellet diet (Ishii et al., 2005a). Because cognitive functions play a key role in animal exploration, in the present study we examined the effect of an exclusively milk formula diet on spatial learning and memory in a water maze and also on induction of long-term potentiation (LTP) and long-term depression (LTD) at the Schaffer collateral-CA1 synapse in the hippocampus. Exclusively milk-fed mice exhibited slower learning and memory deficits in hidden water maze tests as compared with pellet-fed mice. Moreover, milk-fed mice showed a significant inhibition of LTD but a normal induction of LTP. Despite these functional deficits, adult neurogenesis in the dentate gyrus of the hippocampus, which has been proposed to have a causal relationship to spatial memory, was stimulated in milk-fed mice. These result suggest that an exclusively milk formula diet after weaning leads to a stimulation of hippocampal neurogenesis but causes deficits in the induction of LTD in the CA1 hippocampal region and impairment of spatial learning and memory.

Effect of external static magnetic field on the emittance and total charge of electron beams generated by laser-Wakefield acceleration.

Significant enhancement of emittance and an increase of the total charge of femtosecond electron beams produced by a 12 TW, 40 fs laser pulse, tightly focused in a He gas jet, are observed after applying a static magnetic field, B> or =0.2 T, directed along the axis of laser pulse propagation. The effect appears when plasma produced by a laser prepulse becomes magnetized in the vicinity of the focus point: the electron Larmor frequency exceeds the collisional frequency, while periphery of the plasma remains unmagnetized. The entailed change in the shape of the plasma suppresses the diffraction of the main laser pulse that results in a much higher charge of electrons self-injected during the longitudinal wave breaking of the laser wake as well as the excellent stability of the beams.

Observation of strong correlation between quasimonoenergetic electron beam generation by laser wakefield and laser guiding inside a preplasma cavity.

We use a one-shot measurement technique to study effects of laser prepulses on the electron laser wakefield acceleration driven by relativistically intense laser pulses (lambda=790 nm, 11 TW, 37 fs) in dense helium gas jets. A quasimonoenergetic electron bunch with an energy peak approximately 11.5 MeV[DeltaE/E approximately 10% (FWHM)] and with a narrow-cone angle (0.04pi mm mrad) of ejection is detected at a plasma density of 8 x 10(19) cm(-3). A strong correlation between the generation of monoenergetic electrons and optical guiding of the pulse in a thin channel produced by picosecond laser prepulses is observed. This generation mechanism is well corroborated by two-dimensional particle-in-cell simulations.

Effect of a laser prepulse on a narrow-cone ejection of MeV electrons from a gas jet irradiated by an ultrashort laser pulse.

Spatial and energy distributions of energetic electrons produced by an ultrashort, intense laser pulse with a short focal length optical system (Ti:sapphire, 12 TW, 50 fs, lambda=790 nm, f/3.5) in a He gas jet are measured. They are shown to depend strongly on the contrast ratio and shape of the laser prepulse. The wave breaking of the plasma waves at the front of the shock wave formed by a proper laser prepulse is found to make a narrow-cone (0.1pi mm mrad) electron injection. These electrons are further accelerated by the plasma wake field generated by the laser pulse up to tens of MeV forming a Maxwell-like energy distribution. In the case of nonmonotonic prepulse, hydrodynamic instability at the shock front leads to a broader, spotted spatial distribution. The numerical analysis based on a two-dimensional (2D) hydrodynamic (for the laser prepulse) and 2D particle-in-cell (PIC) simulation justifies the mechanism of electron acceleration. The PIC calculation predicts that electrons with energy from 10 to 40 MeV form a bunch with a pulse duration of about 40 fs.