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Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2 weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3 weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders.

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Introduction: Startle habituation and prepulse inhibition (PPI) are distinct measures of different sensory information processes, yet both result in the attenuation of the startle reflex. Identifying startle habituation and PPI neural mechanisms in humans has mostly evolved from acoustic-focused rodent models. Human functional magnetic resonance imaging (fMRI) studies have used tactile startle paradigms to avoid the confounding effects of gradient-related acoustic noise on auditory paradigms and blood-oxygen-level-dependent (BOLD) measures. This study aimed to examine the neurofunctional basis of acoustic startle habituation and PPI in humans with silent fMRI. Methods: Using silent fMRI and simultaneous electromyography (EMG) to measure startle, the neural correlates of acoustic short-term startle habituation and PPI [stimulus onset asynchronies (SOA) of 60 ms and 120 ms] were investigated in 42 healthy adults (28 females). To derive stronger inferences about brain-behaviour correlations at the group-level, models included EMG-assessed measures of startle habituation (regression slope) or PPI (percentage) as a covariate. A linear temporal modulator was modelled at the individual-level to characterise functional changes in neural activity during startle habituation. Results: Over time, participants showed a decrease in startle response (habituation), accompanied by decreasing thalamic, striatal, insula, and brainstem activity. Startle habituation was associated with the linear temporal modulation of BOLD response amplitude in several regions, with thalamus, insula, and parietal lobe activity decreasing over time, and frontal lobe, dorsal striatum, and posterior cingulate activity increasing over time. The paradigm yielded a small amount of PPI (9-13%). No significant neural activity for PPI was detected. Discussion: Startle habituation was associated with the thalamus, putamen, insula, and brainstem, and with linear BOLD response modulation in thalamic, striatal, insula, parietal, frontal, and posterior cingulate regions. These findings provide insight into the mediation and functional basis of the acoustic primary startle circuit. Instead, whilst reduced compared to conventional MRI, scanner noise may have disrupted prepulse detection and processing, resulting in low PPI and impacting our ability to map its neural signatures. Our findings encourage optimisation of the MRI environment for acoustic PPI-based investigations in humans. Combining EMG and functional neuroimaging methods shows promise for mapping short-term startle habituation in healthy and clinical populations.

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The sensorimotor gating is a nervous system function that modulates the acoustic startle response (ASR). Prepulse inhibition (PPI) phenomenon is an operational measure of sensorimotor gating, defined as the reduction of ASR when a high intensity sound (pulse) is preceded in milliseconds by a weaker stimulus (prepulse). Brainstem nuclei are associated with the mediation of ASR and PPI, whereas cortical and subcortical regions are associated with their modulation. However, it is still unclear how the modulatory units can influence PPI. In the present work, we developed a computational model of a neural circuit involved in the mediation (brainstem units) and modulation (cortical and subcortical units) of ASR and PPI. The activities of all units were modeled by the leaky-integrator formalism for neural population. The model reproduces basic features of PPI observed in experiments, such as the effects of changes in interstimulus interval, prepulse intensity, and habituation of ASR. The simulation of GABAergic and dopaminergic drugs impaired PPI by their effects over subcortical units activity. The results show that subcortical units constitute a central hub for PPI modulation. The presented computational model offers a valuable tool to investigate the neurobiology associated with disorder-related impairments in PPI.

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BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk. METHODS: Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers. RESULTS: Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed. CONCLUSIONS: Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.

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BACKGROUND: Rats with a loss-of-function mutation in the contactin-associated protein-like 2 (Cntnap2) gene have been validated as an animal model of autism spectrum disorder (ASD). Similar to many autistic individuals, Cntnap2 knock-out rats (Cntnap2-⁣/-) are hyperreactive to sound as measured through the acoustic startle response. The brainstem region that mediates the acoustic startle response is the caudal pontine reticular nucleus (PnC), specifically giant neurons in the PnC. We previously reported a sex-dependent genotypic effect in the sound-evoked neuronal activity recorded from the PnC, whereby female Cntnap2-⁣/- rats had a dramatic increase in sound-evoked responses compared with wildtype counterparts, but male Cntnap2-⁣/- rats showed only a modest increase in PnC activity that cannot fully explain the largely increased startle in male Cntnap2-⁣/- rats. The present study therefore investigates activation and histological properties of PnC giant neurons in Cntnap2-⁣/- rats and wildtype littermates. METHODS: The acoustic startle response was elicited by presenting rats with 95 dB startle pulses before rats were euthanized. PnC brain sections were stained and analyzed for the total number of PnC giant neurons and the percentage of giant neurons that expressed phosphorylated cAMP response element binding protein (pCREB) in response to startle stimuli. Additionally, in vitro electrophysiology was conducted to assess the resting state activity and intrinsic properties of PnC giant neurons. RESULTS: Wildtype and Cntnap2-⁣/- rats had similar total numbers of PnC giant neurons and similar levels of baseline pCREB expression, as well as similar numbers of giant neurons that were firing at rest. Increased startle magnitudes in Cntnap2-⁣/- rats were associated with increased percentages of pCREB-expressing PnC giant neurons in response to startle stimuli. Male rats had increased pCREB-expressing PnC giant neurons compared with female rats, and the recruited giant neurons in males were also larger in soma size. CONCLUSIONS: Recruitment and size of PnC giant neurons are important factors for regulating the magnitude of the acoustic startle response in Cntnap2-⁣/- rats, particularly in males. These findings allow for a better understanding of increased reactivity to sound in Cntnap2-⁣/- rats and in CNTNAP2-associated disorders such as ASD.

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Sound elicits rapid movements of muscles in the face, ears, and eyes that protect the body from injury and trigger brain-wide internal state changes. Here, we performed quantitative facial videography from mice resting atop a piezoelectric force plate and observed that broadband sounds elicited rapid and stereotyped facial twitches. Facial motion energy (FME) adjacent to the whisker array was 30 dB more sensitive than the acoustic startle reflex and offered greater inter-trial and inter-animal reliability than sound-evoked pupil dilations or movement of other facial and body regions. FME tracked the low-frequency envelope of broadband sounds, providing a means to study behavioral discrimination of complex auditory stimuli, such as speech phonemes in noise. Approximately 25% of layer 5-6 units in the auditory cortex (ACtx) exhibited firing rate changes during facial movements. However, FME facilitation during ACtx photoinhibition indicated that sound-evoked facial movements were mediated by a midbrain pathway and modulated by descending corticofugal input. FME and auditory brainstem response (ABR) thresholds were closely aligned after noise-induced sensorineural hearing loss, yet FME growth slopes were disproportionately steep at spared frequencies, reflecting a central plasticity that matched commensurate changes in ABR wave 4. Sound-evoked facial movements were also hypersensitive in Ptchd1 knockout mice, highlighting the use of FME for identifying sensory hyper-reactivity phenotypes after adult-onset hyperacusis and inherited deficiencies in autism risk genes. These findings present a sensitive and integrative measure of hearing while also highlighting that even low-intensity broadband sounds can elicit a complex mixture of auditory, motor, and reafferent somatosensory neural activity.

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The larval zebrafish is a highly versatile model across research disciplines, and the expanding use of behavioral analysis has contributed to many advances in neuropsychiatric, developmental, and toxicological studies, often through large-scale chemical and genetic screens. In the absence of standardized approaches to larval zebrafish behavior analysis, however, it is critical to understand the impact on behavior of experimental variables such as the size of testing arenas and the choice of embryo medium. Using a custom-built, modular high-throughput testing system, we examined the effects of 4 testing arena sizes and 11 types of embryo media on conserved sensorimotor behaviors in zebrafish larvae. Our data show that testing arena size impacts acoustic startle sensitivity and kinematics, as well as spontaneous locomotion and thigmotaxis, with fish tested in larger arenas displaying reduced startle sensitivity and increased locomotion. We also find that embryo media can dramatically affect startle sensitivity, kinematics, habituation, and prepulse inhibition, as well as spontaneous swimming, turning, and overall activity. Common medium components such as methylene blue and high calcium concentration consistently reduced startle sensitivity and locomotion. To further address how the choice of embryo medium can impact phenotype expression in zebrafish models of disease, we reared chd7 mutant larvae, a model of CHARGE syndrome with previously characterized morphological and behavioral phenotypes, in five different types of media and observed impacts on all phenotypes. By defining the effects of these key extrinsic factors on larval zebrafish behavior, these data can help researchers select the most appropriate conditions for their specific research questions, particularly for genetic and chemical screens.

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Early life adversity in the form of childhood maltreatment in humans or as modeled by maternal separation (MS) in rodents is often associated with an earlier emergence of puberty in females. Earlier pubertal initiation is an example of accelerated biological aging and predicts later risk for anxiety in women, especially in populations exposed to early life trauma. Here we investigated external pubertal markers as well as hypothalamic gene expression of pubertal regulators kisspeptin and gonadotropin-releasing hormone, to determine a biological substrate for MS-induced accelerated puberty. We further investigated a mechanism by which developmental stress might regulate pubertal timing. As kisspeptin and gonadotropin-releasing hormone secretion are typically inhibited by corticotropin releasing hormone at its receptor CRH-R1, we hypothesized that MS induces a downregulation of Crhr1 gene transcription in a cell-specific manner. Finally, we explored the association between pubertal timing and anxiety-like behavior in an acoustic startle paradigm, to drive future preclinical research linking accelerated puberty and anxiety. We replicated previous findings that MS leads to earlier puberty in females but not males, and found expression of kisspeptin and gonadotropin-releasing hormone mRNA to be prematurely increased in MS females. RNAscope confirmed increased expression of these genes, and further revealed that kisspeptin-expressing neurons in females were less likely to express Crhr1 after MS. Early puberty was associated with higher acoustic startle magnitude in females. Taken together, these findings indicate precocial maturation of central pubertal timing mechanisms after MS, as well as a potential role of CRH-R1 in these effects and an association with a translational measure of anxiety.

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In emergency medical services, paramedics are informed of an emergency call by a high-intensity acoustic alarm called the "call alert." Sudden, loud sounds like the call alert may cause a startle response and be experienced as aversive. Studies have identified an association between the call alert and adverse health effects in first responders; conceivably, these adverse health effects might be reduced by modifying the call alert to blunt its startling and aversive properties. Here, we assessed whether the call alert causes a startle response and whether its startling and aversive properties are reduced when the call alert is preceded by a weak acoustic "prepulse," a process referred to as "prepulse inhibition" (PPI). Paramedics (n = 50; 34M:13F:3 not reported; ages 20-68) were exposed to four call alerts (two with and two without a prepulse) in counterbalanced order. Responses were measured using electromyography (measuring blink amplitude), visual analog scales (quantifying perceived call alert intensity and aversiveness), and an electrocardiogram (assessing heart rate). Paramedics responded to the call alert with a startle reflex blink and an increased heart rate. Acoustic prepulses significantly reduced the amplitude of the call alert-induced startle blink, the perceived sound intensity, and the perceived "dislike" of the call alert. These findings confirm that the call alert is associated with an acoustic startle response in paramedics; adding a prepulse to the call alert can reduce its startling and aversive properties. Conceivably, such reductions might also diminish adverse health effects associated with the call alert in first responders.

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Rodent models of behavior used in the fields of neuroscience and psychology generate a wealth of multimodal data. For instance, as a rodent moves and behaves in its environment, muscle contractions apply subtle forces to any surface the animal contacts. These forces generate acoustic waves that propagate through the waveguide as Lamb and shear horizontal (SH) waves and contain information about the rodent's physiology, behavior, and underlying psychological state. If the information in these waves were to be tapped, it would provide a novel, non-invasive way to study rodent behavior. This article lays the foundations for using guided ultrasonic waves generated by a mouse's movement on an aluminum plate for detecting behavior and drawing inferences about acoustic startle responses. The experimental setup involves piezoelectric sensors capturing the waves generated by the rodent's movement, which are then stored as discrete acoustic emission (AE) hits using an amplitude threshold-based data acquisition system. This method of data acquisition ensures that data collection occurs only when the animal moves or behaves, and each movement/behavior is represented by values of features within the generated wavepackets (AE hits). Through open field tests with C57BL/6J mice, utilizing piezoelectric sensors and the DAQ system, it was observed that every movement/behavior of the animal generated Lamb wavepackets within the frequency range of 20 kHz to 100 kHz. Furthermore, rearing behavior in the animals also led to the generation of SH wavepackets in the frequency range of 75 kHz to 230 kHz. This criterion was subsequently employed to detect rearing behavior. In the acoustic startle response test, where the animals' responses to intense sound pulse were recorded, AE hits' features proved useful in quantifying the response. These experimental findings validate the proposed technology's practicality and demonstrate its capability to enhance studies of rodent behavior.

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Objectives: The objective assessment tests overcome the variability of subjective methods. Cortical recordings with gap pre-pulse inhibition of the acoustic startle reflex stimulus have been used as objective tinnitus assessments in humans. This study aims to investigate this possible objective tinnitus test and compare gap-induced inhibition in different stimulus parameters and brain regions. Materials & Methods: Twenty People (18-50 years old) without hearing loss and tinnitus were included. The sound stimuli consisted of continuous background noise with a loud startle tone preceded by a silent gap (20 and 40 ms duration, 120 and 150 ms distance from the startle). The N1-P2 complex amplitude and topoplot maps were extracted in 27-channel cortical response recording after signal processing. Four brain regions of interest (ROI) of anterior-frontal, centro-frontal, right, and left temporal were investigated. Results: The results showed that the maximum inhibition occurred in a 40 ms gap duration and 150 ms distance in all 4 ROIs. In comparing ROIs, the centro-frontal and left temporal regions revealed the most inhibition (p<0.05). The decrease in the amplitude of the N1 and P2 in that region could also be traced in the 100 and 200 ms topoplots. Conclusion: Gap-induced inhibition was observed in all gap-embedded stimuli and all ROIs. However, the 40-150 mode and centro-frontal and left temporal regions had maximum inhibition in normal subjects. It provides a promising tool for objectively assessing tinnitus in humans with particular implications in children.

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Noise-induced tinnitus is generally associated with hearing impairment caused by traumatic acoustic overexposure. Previous studies in laboratory animals and human subjects, however, have observed differences in tinnitus susceptibility, even among individuals with similar hearing loss. The mechanisms underlying increased sensitivity or, conversely, resistance to tinnitus are still incompletely understood. Here, we used behavioral tests and ABR audiometry to compare the sound-evoked responses of mice that differed in the presence of noise-induced tinnitus. The aim was to find a specific pre-exposure neurophysiological marker that would predict the development of tinnitus after acoustic trauma. Noise-exposed mice were screened for tinnitus-like behavior with the GPIAS paradigm and subsequently divided into tinnitus (+T) and non-tinnitus (-T) groups. Both groups showed hearing loss after exposure, manifested by elevated audiometric thresholds along with reduced amplitudes and prolonged latencies of ABR waves. Prior to exposure, except for a slightly increased slope of growth function for ABR amplitudes in +T mice, the two groups did not show significant audiometric differences. Behavioral measures, such as the magnitude of the acoustic startle response and its inhibition by gap pre-pulse, were also similar before exposure in both groups. However, +T mice showed significantly increased suppression of the acoustic startle response in the presence of background noise of moderate intensity. Thus, increased modulation of startle by background sounds may represent a behavioral correlate of susceptibility to noise-induced tinnitus, and its measurement may form the basis of a simple non-invasive method for predicting tinnitus development in laboratory rodents.

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The larval zebrafish is a highly versatile model across research disciplines, and the expanding use of behavioral analysis has contributed to many advances in neuro-psychiatric, developmental, and toxicological studies, often through large-scale chemical and genetic screens. In the absence of standardized approaches to larval zebrafish behavior analysis, however, it is critical to understand the impact on behavior of experimental variables such as the size of testing arenas and the choice of embryo medium. Using a custom-built, modular high-throughput testing system, we examined the effects of 4 testing arena sizes and 11 types of embryo media on conserved sensorimotor behaviors in zebrafish larvae. Our data show that testing arena size impacts acoustic startle sensitivity and kinematics as well as spontaneous locomotion and thigmotaxis, with fish tested in larger arenas displaying reduced startle sensitivity and increased locomotion. We also find that embryo media can dramatically affect startle sensitivity, kinematics, habituation, and pre-pulse inhibition, as well as spontaneous swimming, turning, and overall activity. Common media components such as methylene blue and high calcium concentration consistently reduced startle sensitivity and locomotion. To further address how the choice of embryo medium can impact phenotype expression in zebrafish models of disease, we reared chd7 mutant larvae, a model of CHARGE syndrome with previously characterized morphological and behavioral phenotypes, in 5 different types of media and observed impacts on all phenotypes. By defining the effects of these key extrinsic factors on larval zebrafish behavior, these data can help researchers select the most appropriate conditions for their specific research questions, particularly for genetic and chemical screens.

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The study of fear extinction has been driven largely by Pavlovian fear conditioning methods across the translational spectrum. The primary methods used to study these processes in humans have been recordings of skin conductance (historically termed galvanic skin response) and fear-potentiation of the acoustic startle reflex. As outlined in the following chapter, the combined corpus of this work has demonstrated the value of psychophysiology in better understanding the underlying neurobiology of extinction learning in healthy humans as well as those with psychopathologies. In addition, psychophysiological approaches, which allow for the preservation of methods between species, have shown their applicability to the assessment of wide-ranging treatment effects. The chapter concludes with potential trajectories for future study in this area.

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Calcification of the cerebral microvessels in the basal ganglia in the absence of systemic calcium and phosphate imbalance is a hallmark of primary familial brain calcification (PFBC), a rare neurodegenerative disorder. Mutation in genes encoding for sodium-dependent phosphate transporter 2 (SLC20A2), xenotropic and polytropic retrovirus receptor 1 (XPR1), platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor beta (PDGFRB), myogenesis regulating glycosidase (MYORG), and junctional adhesion molecule 2 (JAM2) are known to cause PFBC. Loss-of-function mutations in XPR1, the only known inorganic phosphate exporter in metazoans, causing dominantly inherited PFBC was first reported in 2015 but until now no studies in the brain have addressed whether loss of one functional allele leads to pathological alterations in mice, a commonly used organism to model human diseases. Here we show that mice heterozygous for Xpr1 (Xpr1WT/lacZ ) present with reduced inorganic phosphate levels in the cerebrospinal fluid and age- and sex-dependent growth of vascular calcifications in the thalamus. Vascular calcifications are surrounded by vascular basement membrane and are located at arterioles in the smooth muscle layer. Similar to previously characterized PFBC mouse models, vascular calcifications in Xpr1WT/lacZ mice contain bone matrix proteins and are surrounded by reactive astrocytes and microglia. However, microglial activation is not confined to calcified vessels but shows a widespread presence. In addition to vascular calcifications, we observed vessel tortuosity and transmission electron microscopy analysis revealed microangiopathy-endothelial swelling, phenotypic alterations in vascular smooth muscle cells, and thickening of the basement membrane.

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Rats emit ultrasonic vocalizations (USV). During aversive situations, rats emit 22-kHz USV, which are considered "alarm calls" and supposed to reflect a negative affective state of the sender. During appetitive situations, rats emit 50-kHz USV, which are believed to reflect a positive affective state. Here, we recorded USV emission in adult male rats during the acoustic startle response test. Our results indicate varied USV emission in both the 22- and 50-kHz USV ranges. Enhanced startle responses were observed in rats with a predominant 22-kHz call profile, supporting the notion that 22-kHz USV emission is associated with a negative affective state.

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BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal interstitial-deletion disorder, occurring in approximately 1 in 2000 to 6000 live births. Affected individuals exhibit variable clinical phenotypes that can include velopharyngeal anomalies, heart defects, T-cell-related immune deficits, dysmorphic facial features, neurodevelopmental disorders, including autism, early cognitive decline, schizophrenia, and other psychiatric disorders. Developing comprehensive treatments for 22q11.2DS requires an understanding of both the psychophysiological and neural mechanisms driving clinical outcomes. Our project probes the core psychophysiological abnormalities of 22q11.2DS in parallel with molecular studies of stem cell-derived neurons to unravel the basic mechanisms and pathophysiology of 22q11.2-related psychiatric disorders, with a primary focus on psychotic disorders. Our study is guided by the central hypothesis that abnormal neural processing associates with psychophysiological processing and underlies clinical diagnosis and symptomatology. Here, we present the scientific background and justification for our study, sharing details of our study design and human data collection protocol. METHODS: Our study is recruiting individuals with 22q11.2DS and healthy comparison subjects between the ages of 16 and 60 years. We are employing an extensive psychophysiological assessment battery (e.g., EEG, evoked potential measures, and acoustic startle) to assess fundamental sensory detection, attention, and reactivity. To complement these unbiased measures of cognitive processing, we will develop stem-cell derived neurons and examine neuronal phenotypes relevant to neurotransmission. Clinical characterization of our 22q11.2DS and control participants relies on diagnostic and research domain criteria assessments, including standard Axis-I diagnostic and neurocognitive measures, following from the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and the North American Prodrome Longitudinal Study (NAPLS) batteries. We are also collecting measures of autism spectrum (ASD) and attention deficit/hyperactivity disorder (ADHD)-related symptoms. DISCUSSION: Studying 22q11.2DS in adolescence and adulthood via deep phenotyping across multiple clinical and biological domains may significantly increase our knowledge of its core disease processes. Our manuscript describes our ongoing study's protocol in detail. These paradigms could be adapted by clinical researchers studying 22q11.2DS, other CNV/single gene disorders, or idiopathic psychiatric syndromes, as well as by basic researchers who plan to incorporate biobehavioral outcome measures into their studies of 22q11.2DS.

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This article presents a low-cost and flexible software solution for acoustic startle response (ASR) test that can be used with a Spike2-based interface. ASR is a reflexive response to an unexpected, loud acoustic stimulus, and prepulse inhibition (PPI) is a phenomenon in which the startle response is reduced when preceded by a weak prestimulus of the same modality. Measuring PPI is important because changes in PPI have been observed in patients with various psychiatric and neurological disorders. Commercial ASR testing systems are expensive, and their closed source code affects their transparency and result reproducibility. The proposed software is easy to install and use. The Spike2 script is customizable and supports a wide range of PPI protocols. As an example of PPI recording, the article presents data obtained in female rats, both wild-type (WT) and dopamine transporter knockout (DAT-KO), showing the same tendency as the data obtained in males, with ASR on a single pulse higher than ASR on prepulse+pulse, and PPI reduced in DAT-KO rats compared to WT.

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The Zwicker tone illusion - an auditory phantom percept after hearing a notched noise stimulus - can serve as an interesting model for acute tinnitus. Recent mechanistic models suggest that the underlying neural mechanisms of both percepts are similar. To date it is not clear if animals do perceive the Zwicker tone, as up to now no behavioral paradigms are available to objectively assess the presence of this phantom percept. Here we introduce, for the first time, a modified version of the gap pre-pulse inhibition of the acoustic startle reflex (GPIAS) paradigm to test if it is possible to induce a Zwicker tone percept in our rodent model, the Mongolian gerbil. Furthermore, we developed a new aversive conditioning learning paradigm and compare the two approaches. We found a significant increase in the GPIAS effect when presenting a notched noise compared to white noise gap pre-pulse inhibition, which is consistent with the interpretation of a Zwicker tone percept in these animals. In the aversive conditioning learning paradigm, no clear effect could be observed in the discrimination performance of the tested animals. When investigating the first 33% of the correct conditioned responses, an effect of a possible Zwicker tone percept can be seen, i.e. animals show identical behavior as if a pure tone was presented, but the paradigm needs to be further improved. Nevertheless, the results indicate that Mongolian gerbils are able to perceive a Zwicker tone and can serve as a neurophysiological model for human tinnitus generation.

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Background: Because it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood. Objectives: To explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks. Methods: Twenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30-130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The ß values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses. Results: Separate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed. Conclusion: The right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.