Prepulse Intensity Research Articles

Relationship of the Acoustic Startle Response and Its Modulation to Adaptive and Maladaptive Behaviors in Typically Developing Children and Those With Autism Spectrum Disorders: A Pilot Study.

Background: Autism spectrum disorder (ASD) is associated with persistent impairments in adaptive functioning across multiple domains of daily life. Thus, investigation of the biological background of both adaptive and maladaptive behaviors may shed light on developing effective interventions for improving social adaptation in ASD. In this study, we examined the relationship between adaptive/maladaptive behaviors and the acoustic startle response (ASR) and its modulation, which are promising neurophysiological markers for ASD translational research.Method: We investigated the ASR and its modulation in 11 children with ASD and 18 with typical development (TD), analyzing the relationship between startle measures and adaptive/maladaptive behaviors assessed with the Vineland Adaptive Behavior Scales (VABS) Second Edition.Results: Peak-ASR latency was negatively correlated with the VABS total score and socialization domain score of adaptive behaviors, while the ASR magnitude for relatively weak stimuli of 75–85 dB was positively correlated with VABS maladaptive behavior scores. Prepulse inhibition (PPI) at the prepulse intensity of 70–75 dB was also correlated with VABS maladaptive behavior. However, these relationships did not remain significant after adjustment for multiple comparisons.Conclusions: Our results indicate that the prolonged peak-ASR latency of ASD children might be associated with impairment in the developmental level of adaptive behavior, and that the greater ASR magnitude to relatively weak acoustic stimuli and smaller PPI of ASD children might increase the risk of maladaptive behavior. Future studies that have larger sample sizes will be important for further elucidating the neurophysiological factors that underpin adaptive as well as maladaptive behaviors in ASD.

Pharmacological characterization of JWX-A0108 as a novel type I positive allosteric modulator of α7 nAChR that can reverse acoustic gating deficits in a mouse prepulse inhibition model.

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated Ca2+-permeable homopentameric ion channel implicated in cognition and neuropsychiatric disorders. Pharmacological enhancement of α7 nAChR function has been suggested for improvement of cognitive deficits. In the present study, we characterized a thiazolyl heterocyclic derivative, 6-(2-chloro-6-methylphenyl)-2-((3-fluoro-4-methylphenyl)amino)thiazolo[4,5-d]pyrimidin-7(6H)-one (JWX-A0108), as a novel type I α7 nAChR positive allosteric modulator (PAM), and evaluated its ability to reverse auditory gating and spatial working memory deficits in mice. In Xenopus oocytes expressing human nAChR channels, application of JWX-A0108 selectively enhanced α7 nAChR-mediated inward current in the presence of the agonist ACh (EC50 value = 4.35 ± 0.12 µM). In hippocampal slices, co-application of ACh and JWX-A0108 (10 µM for each) markedly increased both the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded in pyramidal neurons, but JWX-A0108 did not affect GABA-induced current in oocytes expressing human GABAA receptor α1β3γ2 and α5β3γ2 subtypes. In mice with MK-801-induced deficits in auditory gating, administration of JWX-A0108 (1, 3, and 10 mg/kg, i.p.) dose-dependently attenuates MK-801-induced auditory gating deficits in five prepulse intensities (72, 76, 80, 84, and 88 dB). Furthermore, administration of JWX-A0108 (0.03, 0.1, or 0.3 mg/kg, i.p.) significantly reversed MK-801-induced impaired spatial working memory in mice. Our results demonstrate that JWX-A0108 is a novel type I PAM of α7 nAChR, which may be beneficial for improvement of cognitive deficits commonly found in neuropsychiatric disorders such as schizophrenia and Alzheimer's disease.

Dependency of prepulse inhibition deficits on baseline startle reactivity in a mouse model of the human 22q11.2 microdeletion syndrome.

Hemizygous microdeletion at the chromosomal locus 22q11.2 is a copy number variation with strong genetic linkage to schizophrenia and related disorders. This association, along with its phenotypic overlap with the 22q11.2 microdeletion syndrome, has motivated the establishment of Df[h22q11]/+ mice, in which the human 22q11.2 orthologous region is deleted. Previous investigations using this model showed the presence of reduced prepulse inhibition (PPI) of the acoustic startle reflex, a form of sensorimotor gating known to be impaired in a number of psychiatric disorders. Concomitantly to reduced PPI, however, Df[h22q11]/+ mice are also characterized by a robust increase in baseline startle reactivity, which may complicate or confound the interpretation of PPI. Therefore, the present study re-examined the relationship between acoustic startle reactivity and PPI in this mouse model. We found that while PPI is reduced in Df[h22q11]/+ mice when using its relative indexation (ie, % PPI), this deficit is no longer apparent when using the absolute quantification, that is, the direct comparison between pulse-alone and prepulse-plus-pulse conditions with successively increasing prepulse intensities. We further identified marked negative correlations between % PPI and startle reactivity in Df[h22q11]/+ mice. Moreover, when stratifying Df[h22q11]/+ mice into subgroups displaying low- and high-startle reactivity, only the latter subgroup displayed a significant reduction in % PPI. Collectively, our data suggest that alterations in baseline startle reactivity can confound the outcomes and interpretation of PPI in this mouse model of the human 22q11.2 microdeletion syndrome.

Energy enhancement of the target surface electron by using a 200 TW sub-picosecond laser.

One order of magnitude energy enhancement of the target surface electron beams with central energy at 11.5MeV is achieved by using a 200 TW, 500fs laser at an incident angle of 72° with a prepulse intensity ratio of 5×10-6. The experimental results demonstrate the scalability of the acceleration process to high electron energy with a longer (sub-picosecond) laser pulse duration and a higher laser energy (120J). The total charge of the beam is 400±20 pC(E>2.7 MeV). Such a high orientation and mono-energetic electron jet would be a good method to solve the problem of the large beam divergence in fast ignition schemes and to increase the laser energy deposition on the target core.

Acoustic Hyper-Reactivity and Negatively Skewed Locomotor Activity in Children With Autism Spectrum Disorders: An Exploratory Study.

Investigation of objective and quantitative behavioral phenotypes along with neurobiological endophenotypes might lead to increased knowledge of the mechanisms that underlie autism spectrum disorders (ASD). Here, we investigated the association between locomotor dynamics and characteristics of the acoustic startle response (ASR) and its modulation in ASD (n = 14) and typically developing (TD, n = 13) children. The ASR was recorded in response to acoustic stimuli in increments of 10 dB (65–105 dB SPL). We calculated the average ASR magnitude for each stimulus intensity and peak-ASR latency. Locomotor activity was continuously measured with a watch-type actigraph. We examined statistics of locomotor activity, such as mean activity levels and the skewness of activity. Children with ASD had a significantly greater ASR magnitude in response to a weak acoustic stimulus, which reflects acoustic hyper-reactivity. The skewness of all-day activity was significantly more negative in children with ASD than those with TD. Skewness of daytime activity was also more negative, although only of borderline statistical significance. For all children, the higher mean and more negatively skewed daytime activity, reflecting hyperactivity that was associated with sporadic large daytime “troughs,” was significantly correlated with acoustic hyper-reactivity. The more negatively skewed locomotor activity occurring in the daytime was also associated with impaired sensorimotor gating, examined as prepulse inhibition at a prepulse intensity of 70 dB. This comprehensive investigation of locomotor dynamics and the ASR extends our understanding of the neurophysiology that underlies ASD.

Relationships between the acoustic startle response and prepulse inhibition in C57BL/6J mice: a large-scale meta-analytic study

Prepulse inhibition (PPI) is the suppression of a startle reflex response to a startle stimulus that occurs when a weak prepulse stimulus precedes the startle stimulus. PPI is measured to assess sensorimotor gating across species, including humans and rodents. Reduced PPI, which is thought to reflect dysfunction of sensorimotor gating, is reported in patients with psychiatric disorders, such as schizophrenia, bipolar disorder, and post-traumatic stress disorder (PTSD), and in animal models of these disorders. Individual differences in basal startle reactivity occur even in a genetically homogenous group of animals; however, there is limited information regarding whether basal levels of the startle response are associated with variations in PPI levels. Here, to explore the relationship between an acoustic startle response (ASR) and PPI, we performed a meta-analysis of data obtained from more than 1300 C57BL/6J male mice on the influence of an ASR to 110- and 120-dB startle stimuli on the PPI levels of the ASR at 74- and 78-dB prepulse intensities. Examination of scatter plots of the ASR amplitudes and PPI levels followed by correlation analyses indicated that there is no simple linear relationship between the two measures; when mice were divided into three groups on the basis of their startle amplitudes, there were positive correlations between the amplitude of the ASR to the 110-dB stimulus and PPI levels in a group of mice that showed lower ASR amplitudes among the genetically homogenous group, whereas no significant correlations were identified in groups of mice that showed intermediate and higher ASR amplitudes. As indicated by the correlation analysis, the lowest responders to the 110-dB stimulus exhibited lower levels of PPI than the intermediate or higher responders. In contrast, for the 120-dB stimulus, a negative correlation was identified between the amplitude of the ASR to the 120-dB stimulus and the PPI levels in the groups of mice that showed intermediate or higher ASR amplitudes. Lower and intermediate responders showed higher levels of PPI than higher responders to the 120-dB stimulus. These findings suggest that basal startle reactivity may affect PPI levels in male C57BL/6J mice, thus representing one potential confounding factor that may confuse the interpretation of PPI results. These findings emphasize the importance of careful examination of startle reactivity to ensure a reliable assessment of PPI.

Experimental investigation on pulse-contrast degradation caused by surface reflection in optical parametric chirped-pulse amplification

In this Letter, we experimentally explore the pulse-contrast degradation caused by surface reflection in optical parameter chirped-pulse amplification. Different pump-to-signal conversion efficiencies and post-pulses with different intensities are obtained by changing the seed-pulse or pump-pulse energy and inserting etalons with different reflection coefficients, respectively. The contrast measurements show that the generated first pre-pulse intensity is proportional to the product of the surface reflection intensity ratio and the square of the pump-to-signal conversion efficiency.

Dose-dependent and opposite effects of orexin A on prepulse inhibition response in sleep-deprived and non-sleep-deprived rats

Orexin is a novel neurotransmitter released from lateral hypothalamus, that is a crucial modulator in sleep/wakefulness system. Recent studies also suggest its possible role in the neurodevelopmental disorders, such as schizophrenia. Our study consists of two experiments, where we investigate the effect of orexin A (OXA), one of two isoforms of orexin that can pass blood brain barrier, on the prepulse inhibition of acoustic startle reflex. The first experiment tested the effect of OXA on PPI response of non-sleep-deprived rats via intraperitoneal injection 30min before testing. Our results show that 40μg/kg OXA attenuates PPI% at 78dB and 86dB prepulse intensities. The second experiment utilized 72-h REM sleep deprivation, as a model for sleep-deprivation-induced impairment of PPI response. Here, we tested the effect of OXA on PPI% of sleep-deprived rats via intraperitoneal injection at the last 30min of sleep deprivation, testing for PPI immediately afterwards. Our results showed that (1) sleep deprivation attenuates the PPI% at 74dB, 78dB and 86dB prepulse intensities and (2) 10μg/kg OXA completely restores the impaired PPI% at 78dB only, where the highest PPI% impairment was observed. These results suggest that orexin A modulates PPI response in rats in a dose-dependent manner, oppositely for non-sleep-deprived and sleep-deprived rats, and a more detailed investigation for the etiology of this effect should follow.

Evaluation of startle response and prepulse inhibition based on changes in the range of vertical pressure force of the feet on the ground: a preliminary study.

The aim of the study was to evaluate the possibility of estimating a startle response and sensorimotor gating based on changes in the range of vertical pressure force of the feet on the ground during a dynamometric examination. The study encompassed 13 healthy and physically fit men (age: 23.3±2.0years; height: 178.0±6.1cm; and weight: 76.1±9.0kg). The inhibitory mechanisms of startle reflex were used as the measure of sensorimotor gating. It was triggered by a strong acoustic stimulus (106dB SPL, 40ms), which was preceded by a similar, weaker signal (80dB SPL, 20ms). Startle reflex was evaluated using a piezoelectric force platform. The results of the conducted study show that the range of vertical pressure force of the feet caused by the reaction to a strong acoustic stimulus is significantly smaller when this stimulus is preceded by a signal of lower intensity (prepulse). Such assessment is only possible with the participants' eyes open. The generalized startle response of a person may be estimated using a force platform, based on changes in the range of vertical pressure force of the feet on the ground, which are caused by unexpected acoustic stimuli. There is a strong indication that using a force platform to evaluate sensorimotor gating could be used as an alternative to electromyographic examinations.

Increased risk of developing schizophrenia in animals exposed to cigarette smoke during the gestational period

Cigarette smoking during the prenatal period has been investigated as a causative factor of obstetric abnormalities, which lead to cognitive and behavioural changes associated with schizophrenia. The aim of this study was to investigate behaviour and AChE activity in brain structures in adult rats exposed to cigarette smoke during the prenatal period. Pregnant rats were divided into non-PCSE (non-prenatal cigarette smoke exposure) and PCSE (prenatal cigarette smoke exposure) groups. On post-natal day 60, the rats received saline or ketamine for 7days and were subjected to behavioural tasks. In the locomotor activity task, the non-PCSE+ketamine and PCSE+ketamine groups exhibited increased locomotor activity compared with the saline group. In the social interaction task, the non-PCSE+ketamine and PCSE+ketamine groups exhibited an increased latency compared with the control groups. However, the PCSE+ketamine group exhibited a decreased latency compared with the non-PCSE+ketamine group, which indicates that the cigarette exposure appeared to decrease, the social deficits generated by ketamine. In the inhibitory avoidance task, the non-PCSE+ketamine, PCSE, and PCSE+ketamine groups exhibited impairments in working memory, short-term memory, and long-term memory. In the pre-pulse inhibition (PPI) test, cigarette smoke associated with ketamine resulted in impaired PPI in 3 pre-pulse (PP) intensity groups compared with the control groups. In the biochemical analysis, the AChE activity in brain structures increased in the ketamine groups; however, the PCSE+ketamine group exhibited an exacerbated effect in all brain structures. The present study indicates that exposure to cigarette smoke during the prenatal period may affect behaviour and cerebral cholinergic structures during adulthood.

Dissociable effects of the d- and l- enantiomers of govadine on the disruption of prepulse inhibition by MK-801 and apomorphine in male Long-Evans rats.

The search for novel antipsychotic drugs to treat schizophrenia is driven by the poor treatment efficacy, serious side effects, and poor patient compliance of current medications. Recently, a class of compounds known as tetrahydroprotoberberines, which includes the compound d,l-govadine, have shown promise in preclinical rodent tests relevant to schizophrenia. To date, the effect of govadine on prepulse inhibition (PPI), a test for sensorimotor gating commonly used to assess the effects of putative treatments for schizophrenia, has not been determined. The objective of the present study was to determine the effects of each enantiomer of govadine (d- and l-govadine) on PPI alone and its disruption by the distinct pharmacological compounds apomorphine and MK-801. Male Long-Evans rats were treated systemically with d- or l-govadine and apomorphine or MK-801 prior to PPI. The PPI paradigm employed here included parametric manipulations of the prepulse intensity and the interval between the prepulse and pulse. Acute MK-801 (0.15mg/kg) significantly increased the startle response to startle pulses alone, while both MK-801 and apomorphine (0.2mg/kg) significantly increased reactivity to prepulse-alone trials. Both MK-801 and apomorphine disrupted PPI. In addition, d-govadine alone significantly disrupted PPI in the apomorphine experiment. Pretreatment with l-, but not d-, govadine (1.0mg/kg) blocked the effect of apomorphine and MK-801 on PPI. Treatment of rats with l-govadine alone (0.3, 1.0, 3.0mg/kg) also dose-dependently increased PPI. Given the high affinity of l-govadine for dopamine D2 receptors, these results suggest that further testing of l-govadine as an antipsychotic is warranted.

Differential effects of antipsychotic and propsychotic drugs on prepulse inhibition and locomotor activity in Roman high- (RHA) and low-avoidance (RLA) rats.

Animal models with predictive and construct validity are necessary for developing novel and efficient therapeutics for psychiatric disorders. We have carried out a pharmacological characterization of the Roman high- (RHA-I) and low-avoidance (RLA-I) rat strains with different acutely administered propsychotic (DOI, MK-801) and antipsychotic drugs (haloperidol, clozapine), as well as apomorphine, on prepulse inhibition (PPI) of startle and locomotor activity (activity cages). RHA-I rats display a consistent deficit of PPI compared with RLA-I rats. The typical antipsychotic haloperidol (dopamine D2 receptor antagonist) reversed the PPI deficit characteristic of RHA-I rats (in particular at 65 and 70dB prepulse intensities) and reduced locomotion in both strains. The atypical antipsychotic clozapine (serotonin/dopamine receptor antagonist) did not affect PPI in either strain, but decreased locomotion in a dose-dependent manner in both rat strains. The mixed dopamine D1/D2 agonist, apomorphine, at the dose of 0.05mg/kg, decreased PPI in RHA-I, but not RLA-I rats. The hallucinogen drug DOI (5-HT2A agonist; 0.1-1.0mg/kg) disrupted PPI in RLA-I rats in a dose-dependent manner at the 70dB prepulse intensity, while in RHA-I rats, only the 0.5mg/kg dose impaired PPI at the 80dB prepulse intensity. DOI slightly decreased locomotion in both strains. Finally, clozapine attenuated the PPI impairment induced by the NMDA receptor antagonist MK-801 only in RLA-I rats. These results add experimental evidence to the view that RHA-I rats represent a model with predictive and construct validity of some dopamine and 5-HT2A receptor-related features of schizophrenia.

Lesions of the paraventricular thalamic nucleus attenuates prepulse inhibition of the acoustic startle reflex

The paraventricular thalamic nucleus (PVT) is a midline nucleus with strong connections to cortical and subcortical brain regions such as the prefrontal cortex, amygdala, nucleus accumbens and hippocampus and receives strong projections from brain stem nuclei. Prepulse inhibition (PPI) is mediated and modulated by complex cortical and subcortical networks that are yet to be fully identified in detail. Here, we suggest that the PVT may be an important brain region for the modulation of PPI. In our study, the paraventricular thalamic nuclei of rats were electrolytically lesioned. Two weeks after the surgery, the PPI responses of the animals were monitored and recorded using measurements of acoustic startle reflex. Our results show that disruption of the PVT dramatically attenuated PPI at prepulse intensities of 74, 78 and 86dB compared to that in the sham lesion group. Thus, we suggest that the PVT may be an important part of the PPI network in the rat brain.

Enhanced X-ray emission from laser-produced gold plasma by double pulses irradiation of nano-porous targets

Enhancement of the soft X-ray emission including free–free, free–bound and bound–bound emissions from Au nano-porous targets irradiated by single and double laser pulses is studied through numerical simulations. Laser pulses of duration 2 ns are used in calculations considering different prepulse intensities and a fixed intensity of 1013 Wcm−2 for the main pulse. The effects of prepulse intensity and time separation between laser pulses are studied for targets of different porosities. Results show that the X-ray yield can be enhanced significantly by a nano-porous target having optimum initial density. Such enhancement can be more improved when double laser pulses with appropriate delay time and intensities irradiate nano-porous targets. It is shown that the enhancement will be reduced when the prepulse intensity is greater than a specific value.

Improved assessment of sensorimotor gating in animal models relevant to ASD: A data modelling approach to quantify PrePulse Inhibition of the acoustic startle reflex

BackgroundThe PrePulse Inhibition (PPI) of the acoustic startle reflex is a neurobehavioral test frequently used in neurodevelopmental studies. Most PPI studies have used rodent models of schizophrenia; however, the currently used data analysis method does not take into account the variability present in autistic preclinical models. New methodWe propose a new data modelling approach for PPI data obtained from animals exposed to valproic acid or endocrine disruptors, using mixed modeling; and a new calculation of inhibition of the acoustic startle, which takes into account the habituation phenomenon. ResultsHabituation, or possibly exhaustion, occurred in all groups. The classic method of calculation of inhibition analysed with ANOVA indicated no group or sex effect for the overall inhibition of startle. In contrast, when analysed using mixed models, group and sex effects were observed. In addition, using the new method of calculation, both statistical analyses showed a sex effect, with females having decreased global inhibition but no group effect. ANOVA generated more false positive results for PPI in relation to prepulse intensities. Comparison with existing methodThe current classic method of analysis of PPI test is a calculation of inhibition based on average startle amplitude throughout the test session and a statistical ANOVA analysis. This method does not take into account habituation/exhaustion and within-subject and −group variability. ConclusionsThe results of this study demonstrate that use of ANOVA analysis leads to misinterpretation of PPI data in autistic preclinical models and we propose a new data analysis adapted to these models.

Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats

Selective serotonin reuptake inhibitors (SSRIs) block the serotonin (5-HT) reuptake transporter (SERT) and increase synaptic 5-HT. 5-HT is also important in brain development; hence when SSRIs are taken during pregnancy there exists the potential for these drugs to affect CNS ontogeny. Prenatal SSRI exposure has been associated with an increased prevalence of autism spectrum disorder (ASD), and peripheral 5-HT is elevated in some ASD patients. Perinatal SSRI exposure in rodents has been associated with increased depression and anxiety-like behavior, decreased sociability, and impaired learning in the offspring, behaviors often seen in ASD. The present study investigated whether perinatal exposure to citalopram causes persistent neurobehavioral effects. Gravid Sprague-Dawley rats were assigned to two groups and subcutaneously injected twice per day with citalopram (10mg/kg; Cit) or saline (Sal) 6h apart on embryonic day (E)6-21, and then drug was given directly to the pups after delivery from postnatal day (P)1-20. Starting on P60, one male/female from each litter was tested in the Cincinnati water maze (CWM) and open-field before and after MK-801. A second pair from each litter was tested in the Morris water maze (MWM) and open-field before and after (+)-amphetamine. A third pair was tested as follows: elevated zero-maze, open-field, marble burying, prepulse inhibition of acoustic startle, social preference, and forced swim. Cit-exposed rats were impaired in the MWM during acquisition and probe, but not during reversal, shift, or cued trials. Cit-exposed rats also showed increased marble burying, decreased time in the center of the open-field, decreased latency to immobility in forced swim, and increased acoustic startle across prepulse intensities with no effects on CWM. The results are consistent with citalopram inducing several ASD-like effects. The findings add to concerns about use of SSRIs during pregnancy. Further research on different classes of antidepressants, dose-effect relationships, timing of exposure periods, and mechanisms for these effects are needed. It is also important to balance the effects described here against the effects of the disorders for which the drugs are given.

Reflexes Inhibited by a Prepulse

Prepulse inhibition refers to the inhibition of the startle reflexes by a weak stimulus (prepulse) that precedes a strong startle stimulus (pulse). Previous findings suggest that prepulse intensity affects prepulse inhibition amplitude and that prepulse inhibition amplitudes vary across onset intervals between the prepulse and pulse. However, evidence regarding the effect of startle stimulus intensity is still inconclusive, especially due to variations between prepulse inhibition scores calculated by using percentage-type and difference-type formulas. Moreover, the combined effect of startle stimulus and prepulse intensities across onset intervals remains poorly understood. The present study investigated the combined effect as well as the influence of startle response amplitudes on the formulae used for the calculation. The results suggest that startle stimulus intensity could potentially affect results of percentage-type formulae for calculating prepulse inhibition over a wide range of lead intervals. Furthermore, the results demonstrated that a combination of strong startle stimulus intensities and weak prepulse intensities could not induce prepulse inhibition at long onset intervals (1000 ms and 2000 ms).

The T-type calcium channel antagonist Z944 disrupts prepulse inhibition in both epileptic and non-epileptic rats

The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure of sensorimotor gating which is a basic process whereby the brain filters incoming stimuli to enable appropriate responding in sensory rich environments. The regulation of PPI involves a network of limbic, cortical, striatal, pallidal and pontine brain areas, many of which show high levels of T-type calcium channel expression. Therefore, we tested the effects of blocking T-type calcium channels on PPI with the potent and selective T-type antagonist Z944 (0.3, 1, 3, 10mg/kg; i.p.) in adult Wistar rats and two related strains, the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and Non-Epileptic Control (NEC). PPI was tested using a protocol that varied prepulse intensity (3, 6, and 12dB above background) and prepulse-pulse interval (30, 50, 80, 140ms). Z944 decreased startle in the Wistar strain at the highest dose relative to lower doses. Z944 dose-dependently disrupted PPI in the Wistar and GAERS strains with the most potent effect observed with the higher doses. These findings suggest that T-type calcium channels contribute to normal patterns of brain activity that regulate PPI. Given that PPI is disrupted in psychiatric disorders, future experiments that test the specific brain regions involved in the regulation of PPI by T-type calcium channels may help inform therapeutic development for those suffering from sensorimotor gating impairments.

Numerical simulations of recent proton acceleration experiments with sub-100 TW laser systems

Recent experiments carried out at the Italian National Research Center, National Optics Institute Department in Pisa, are showing interesting results regarding maximum proton energies achievable with sub-100 TW laser systems. While laser systems are being continuously upgraded in laboratories around the world, at the same time a new trend on stabilizing and making ion acceleration results reproducible is growing in importance. Almost all applications require a beam with fixed performance, so that the energy spectrum and the total charge exhibit moderate shot to shot variations. This result is surely far from being achieved, but many paths are being explored in order to reach it. Some of the reasons for this variability come from fluctuations in laser intensity and focusing, due to optics instability. Other variation sources come from small differences in the target structure. The target structure can vary substantially, when it is impacted by the main pulse, due to the prepulse duration and intensity, the shape of the main pulse and the total energy deposited. In order to qualitatively describe the prepulse effect, we will present a two dimensional parametric scan of its relevant parameters. A single case is also analyzed with a full three dimensional simulation, obtaining reasonable agreement between the numerical and the experimental energy spectrum.

Enhancement of conversion efficiency and spatial coherence of high order harmonics generated from pre-formed plasma plumes using an apertured laser beam

The effect of laser beam aperturing (Ti: sapphire laser; 800 nm, 45 fs) on the conversion efficiency (CE), harmonic yield and spatial coherence of high order harmonics generated from a low excited plasma plume of carbon (neutral and singly charged ions) is studied. The optimization of CE by varying the aperture size in combination with different laser and plasma plume parameters was carried out. The CE of the 15th harmonic is enhanced from ∼10−7 for an unapertured laser beam to ∼10−6 for ∼¼ times the unapertured beam diameter, at same laser energy in both cases. Further, it was found that, at a given aperture size, there is an optimum prepulse intensity for maximum CE. The results are explained by taking into account the theoretical consideration of phase matching issues in plasma plumes. The study shows that tuning the prepulse intensity and aperture size gives an easy handle to increase the harmonic conversion along with its coherence properties. The study will be useful for producing an intense source of harmonics with high spatial coherence from plasmas plumes for applications.