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Physiology & Behavior Oct 2023Rats emit ultrasonic vocalizations (USV). During aversive situations, rats emit 22-kHz USV, which are considered "alarm calls" and supposed to reflect a negative...
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.
Topics: Rats; Male; Animals; Ultrasonics; Vocalization, Animal; Reflex, Startle; Emotions; Affect
PubMed: 37423456
DOI: 10.1016/j.physbeh.2023.114290 -
Journal of Medical Genetics Jan 2024Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%-0.4% of the population. It results from dysregulation of bone homeostasis in the...
BACKGROUND
Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%-0.4% of the population. It results from dysregulation of bone homeostasis in the otic capsule, most commonly leading to fixation of the stapes bone, impairing sound conduction through the middle ear. Otosclerosis has a well-known genetic predisposition including familial cases with apparent autosomal dominant mode of inheritance. While linkage analysis and genome-wide association studies suggested an association with several genomic loci and with genes encoding structural proteins involved in bone formation or metabolism, the molecular genetic pathophysiology of human otosclerosis is yet mostly unknown.
METHODS
Whole-exome sequencing, linkage analysis, generation of CRISPR mutant mice, hearing tests and micro-CT.
RESULTS
Through genetic studies of kindred with seven individuals affected by apparent autosomal dominant otosclerosis, we identified a disease-causing variant in , encoding a key component of the PBAF chromatin remodelling complex. We generated CRISPR-Cas9 transgenic mice carrying the human mutation in the mouse orthologue. Mutant mice exhibited marked hearing impairment demonstrated through acoustic startle response and auditory brainstem response tests. Isolated ossicles of the auditory bullae of mutant mice exhibited a highly irregular structure of the incus bone, and their in situ micro-CT studies demonstrated the anomalous structure of the incus bone, causing disruption in the ossicular chain.
CONCLUSION
We demonstrate that otosclerosis can be caused by a variant in , with a similar phenotype of hearing impairment and abnormal bone formation in the auditory bullae in transgenic mice carrying the human mutation in the mouse orthologue.
Topics: Adult; Humans; Mice; Animals; Otosclerosis; Blister; Genome-Wide Association Study; Reflex, Startle; Hearing Loss; Phenotype; Mice, Transgenic; Mutation; DNA Helicases; Nuclear Proteins; Transcription Factors
PubMed: 37399313
DOI: 10.1136/jmg-2023-109264 -
Perceptual and Motor Skills Oct 2023The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The...
The application of a noxious stimulus reduces the perception of other noxious stimuli, which can be assessed by an experimental method called "counterirritation." The question arises whether this type of inhibition also affects the processing of other aversive (but not nociceptive) stimuli, such as loud tones. If aversiveness or, in other words, negative emotional valence qualifies a stimulus to be affected by counterirritation, the general emotional context may also play a role in modulating counterirritation effects. We involved 63 participants in this study ( age = 38.8, = 10.5 years; 33 males, 30 females). We tried to counterirritate their perceptual and startle reactions to aversively loud tones (105 db) by immersing the hand into a painful hot water bath (46°C) in two emotional valence conditions (i.e., a neutral and a negative valence block in which we showed either neutral pictures or pictures of burn wounds). We assessed Inhibition by loudness ratings and startle reflex amplitudes. Counterirritation significantly reduced both loudness ratings and startle reflex amplitudes. The emotional context manipulation did not affect this clear inhibitory effect, showing that counterirritation by a noxious stimulus affects aversive sensations not induced by nociceptive stimuli. Thus, the assumption that "pain inhibits pain" should be widened to "pain inhibits the processing of aversive stimuli." This broadened understanding of counterirritation leads to a questioning of the postulate of clear pain specificity in paradigms like "conditioned pain modulation" (CPM) or "diffuse noxious inhibitory controls" (DNIC).
Topics: Male; Female; Humans; Adult; Pain; Emotions; Affect; Perception; Pain Perception
PubMed: 37340659
DOI: 10.1177/00315125231183604 -
Neuropsychopharmacology Reports Sep 2023Proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating...
AIM
Proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. This study aimed to examine whether a proinflammatory cytokine, IL-17A, induces impairment in sensorimotor gating in mice. We also examined whether IL-17A administration affects GSK3α/β protein level or phosphorylation in the striatum.
METHODS
Recombinant mouse IL-17A (low-dose: 0.5 ng/mL and high-dose: 50 ng/mL with 10 μL/g mouse body weight, respectively) or vehicle was intraperitoneally administered into C57BL/6 male mice 10 times in 3 weeks (sub-chronic administration). Prepulse inhibition test using acoustic startle stimulus was conducted 4 weeks after the final IL-17A administration. We evaluated the effect of IL-17A administration on protein level or phosphorylation of GSK3α/β in the striatum by using Western blot analysis.
RESULTS
Administration of IL-17A induced significant PPI deterioration. Low-dose of IL-17A administration significantly decreased both GSK3α (Ser21) and GSK3β (Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3α/β protein levels except for GSK3α in low-dose IL-17A administration group.
CONCLUSION
We demonstrated for the first time that sub-chronic IL-17A administration induced PPI disruption and that IL-17A administration resulted in decreased phosphorylation of GSKα/β at the striatum. These results suggest that IL-17A could be a target molecule in the prevention and treatment of sensorimotor gating abnormalities observed in schizophrenia.
Topics: Mice; Male; Animals; Prepulse Inhibition; Reflex, Startle; Interleukin-17; Mice, Inbred C57BL; Acoustics
PubMed: 37280178
DOI: 10.1002/npr2.12351 -
Cognitive, Affective & Behavioral... Aug 2023A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in...
A widely shared framework suggests that anxiety maps onto two dimensions: anxious apprehension and anxious arousal. Previous research linked individual differences in these dimensions to differential neural response patterns in neuropsychological, imaging, and physiological studies. Differential effects of the anxiety dimensions might contribute to inconsistencies in prior studies that examined neural processes underlying anxiety, such as hypersensitivity to unpredictable threat. We investigated the association between trait worry (as a key component of anxious apprehension), anxious arousal, and the neural processing of anticipated threat. From a large online community sample (N = 1,603), we invited 136 participants with converging and diverging worry and anxious arousal profiles into the laboratory. Participants underwent the NPU-threat test with alternating phases of unpredictable threat, predictable threat, and safety, while physiological responses (startle reflex and startle probe locked event-related potential components N1 and P3) were recorded. Worry was associated with increased startle responses to unpredictable threat and increased attentional allocation (P3) to startle probes in predictable threat anticipation. Anxious arousal was associated with increased startle and N1 in unpredictable threat anticipation. These results suggest that trait variations in the anxiety dimensions shape the dynamics of neural processing of threat. Specifically, trait worry seems to simultaneously increase automatic defensive preparation during unpredictable threat and increase attentional responding to threat-irrelevant stimuli during predictable threat anticipation. The current study highlights the utility of anxiety dimensions to understand how physiological responses during threat anticipation are altered in anxiety and supports that worry is associated with hypersensitivity to unpredictable, aversive contexts.
Topics: Humans; Reflex, Startle; Anxiety; Evoked Potentials; Anxiety Disorders; Arousal; Anticipation, Psychological
PubMed: 37106311
DOI: 10.3758/s13415-023-01094-4 -
Psychopharmacology Nov 2023Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear.
METHODS
Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals.
RESULTS
Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT agonists, 5-HT antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT antagonists. No associations were found between drug effects and methodological characteristics, except for strain.
CONCLUSIONS
The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review.
Topics: Animals; Anti-Anxiety Agents; Serotonin; Fear; Anxiety; Benzodiazepines; Reflex, Startle
PubMed: 36651922
DOI: 10.1007/s00213-022-06307-1 -
Attention, Perception & Psychophysics Apr 2024The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena...
The perceived intensity of an intense stimulus as well as the startle reflex it elicits can both be reduced when preceded by a weak stimulus (prepulse). Both phenomena are used to characterise the processes of sensory gating in clinical and non-clinical populations. The latter phenomenon, startle prepulse inhibition (PPI), is conceptualised as a measure of pre-attentive sensorimotor gating due to its observation at short latencies. In contrast, the former, prepulse inhibition of perceived stimulus intensity (PPIPSI), is believed to involve higher-order cognitive processes (e.g., attention), which require longer latencies. Although conceptually distinct, PPIPSI is often studied using parameters that elicit maximal PPI, likely limiting what we can learn about sensory gating's influence on conscious perception. Here, we tested an array of stimulus onset asynchronies (SOAs; 0-602 ms) and prepulse intensities (0-3× perceptual threshold) to determine the time course and sensitivity to the intensity of electrotactile PPIPSI. Participants were required to compare an 'unpleasant but not painful' electric pulse to their left wrist that was presented alone with the same stimulus preceded by an electric prepulse, and report which pulse stimulus felt more intense. Using a 2× perceptual threshold prepulse, PPIPSI emerged as significant at SOAs from 162 to 602 ms. We conclude that evidence of electrotactile PPIPSI at SOAs of 162 ms or longer is consistent with gating of perception requiring higher-level processes, not measured by startle PPI. The possible role of attentional processes, stimuli intensity, modality-specific differences, and methods of investigating PPIPSI further are discussed.
Topics: Humans; Reflex, Startle; Male; Female; Adult; Young Adult; Prepulse Inhibition; Sensory Gating; Attention; Sensory Thresholds; Electric Stimulation; Touch Perception; Reaction Time
PubMed: 36385671
DOI: 10.3758/s13414-022-02597-x