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Biology Letters Jul 2023Boldness, the way an individual reacts to risk, is a commonly studied personality trait in animals. Consistent among-individual differences in startle response durations...
Boldness, the way an individual reacts to risk, is a commonly studied personality trait in animals. Consistent among-individual differences in startle response durations (latency to recover from a startling stimulus) are frequently assumed to reflect variation in boldness. An alternative explanation is that these latencies are not directly driven by variation in responses to information on risk, but by underlying differences in dynamic performance capacities. Here we investigate this possibility by analysing relationships between locomotory speed, a measure of whole-body dynamic performance capacity in hermit crabs, and startle response duration, a repeatable latency measure used as an index of boldness. Individuals differed in mean startle response duration, in the consistency of their startle responses, in their reaction norms across repeated observations, and mean startle responses increased with crab mass. However, there were no relationships between startle responses and locomotory speed. This indicates that startle responses do not reflect underlying performance capacities and suggests that they provide insight into differences in how individuals respond to risky situations. Since similar latencies are used as measures of boldness in other animals, we suggest that potential relationships between apparent boldness and performance capacity should be tested.
Topics: Animals; Behavior, Animal; Anomura; Reflex, Startle
PubMed: 37490943
DOI: 10.1098/rsbl.2023.0224 -
Scientific Reports Jul 2023During embryonic development, heterozygous mutant kreisler mice undergo ectopic expression of the Hoxa3 gene in the rostral hindbrain, affecting the opioid and...
During embryonic development, heterozygous mutant kreisler mice undergo ectopic expression of the Hoxa3 gene in the rostral hindbrain, affecting the opioid and noradrenergic systems. In this model, we have investigated behavioral and cognitive processes in their adulthood. We confirmed that pontine and locus coeruleus neuronal projections are impaired, by using startle and pain tests and by analyzing immunohistochemical localization of tyrosine hydroxylase. Our results showed that, even if kreisler mice are able to generate eyelid reflex responses, there are differences with wild-types in the first component of the response (R1), modulated by the noradrenergic system. The acquisition of conditioned motor responses is impaired in kreisler mice when using the trace but not the delay paradigm, suggesting a functional impairment in the hippocampus, subsequently confirmed by reduced quantification of alpha2a receptor mRNA expression in this area but not in the cerebellum. Moreover, we demonstrate the involvement of adrenergic projection in eyelid classical conditioning, as clonidine prevents the appearance of eyelid conditioned responses in wild-type mice. In addition, hippocampal motor learning ability was restored in kreisler mice by administration of adrenergic antagonist drugs, and a synergistic effect was observed following simultaneous administration of idazoxan and naloxone.
Topics: Mice; Animals; Conditioning, Classical; Neurons; Conditioning, Eyelid; Eyelids; Rhombencephalon; Homeodomain Proteins
PubMed: 37454229
DOI: 10.1038/s41598-023-38278-4 -
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 -
Cureus Apr 2023Hyperekplexia (HK) or startle disease is an uncommon, early infantile onset, potentially treatable neurogenetic disorder. It is characterized by an exaggerated startle...
Hyperekplexia (HK) or startle disease is an uncommon, early infantile onset, potentially treatable neurogenetic disorder. It is characterized by an exaggerated startle reflex in response to tactile or acoustic or visual stimuli followed by generalized hypertonia. It is caused by genetic mutations in a number of different genes such as , , , , and . HK is frequently misdiagnosed as a form of epilepsy and is advised for prolonged antiseizure medications. Here, we report a two-month-old female child with HK, who was treated for epilepsy. Next-generation sequencing revealed a pathogenic homozygous missense mutation of variant c.1259C>A in exon 9 of the gene that was compatible with the diagnosis of hyperekplexia-1.
PubMed: 37252475
DOI: 10.7759/cureus.38082 -
Translational Psychiatry May 2023The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was...
The consumption of synthetic cannabinoids during adolescence is reported to be a risk factor for the appearance of psychiatric disorders later in life. JWH-018 was identified as one of the primary psychoactive components present in Spice/K2 preparations. This study evaluated the short- and long-term consequences of exposure to JWH-018 during the adolescence in anxiety-like behavior, fear extinction, and sensorimotor gating in male and female mice. Alterations in anxiety varied depending on the time interval between treatment and behavioral analysis along with sex, while no changes were observed in the extinction of fear memory. A decrease in prepulse inhibition of the startle reflex was revealed in male, but not female, mice at short- and long-term. This behavioral disturbance was associated with a reduction in the number of perineuronal nets in the prelimbic and infralimbic regions of the prefrontal cortex in the short-term. Furthermore, adolescent exposure to JWH-018 induced an activation of microglia and astrocytes in the prefrontal cortex of male mice at both time intervals. A transitory decrease in the expression of GAD67 and CB2 cannabinoid receptors in the prefrontal cortex was also found in male mice exposed to JWH-018. These data reveal that the treatment with JWH-018 during the adolescence leads to long-lasting neurobiological changes related to psychotic-like symptoms, which were sex-dependent.
Topics: Male; Animals; Mice; Cannabinoids; Extinction, Psychological; Fear; Prepulse Inhibition
PubMed: 37225721
DOI: 10.1038/s41398-023-02469-4 -
Neurobiology of Stress May 2023Animal models of maternal immune activation (MIA) are central to identifying the biological mechanisms that underly the association between prenatal infection and...
Maternal immune activation alters placental histone-3 lysine-9 tri-methylation, offspring sensorimotor processing, and hypothalamic transposable element expression in a sex-specific manner.
Animal models of maternal immune activation (MIA) are central to identifying the biological mechanisms that underly the association between prenatal infection and neuropsychiatric disorder susceptibility. Many studies, however, have limited their scope to protein coding genes and their role in mediating this inherent risk, while much less attention has been directed towards exploring the roles of the epigenome and transposable elements (TEs). In Experiment 1, we demonstrate the ability of MIA to alter the chromatin landscape of the placenta. We induced MIA by injecting 200 μg/kg (i.p.) of lipopolysaccharide (LPS) on gestational day 15 in Sprague-Dawley rats. We found a sex-specific rearrangement of heterochromatin 24-h after exposure to MIA, as evidenced by an increase in histone-3 lysine-9 trimethylation (H3K9me3). In Experiment 2, MIA was associated with long-term sensorimotor processing deficits as indicated by reduced prepulse inhibition (PPI) of the acoustic startle reflex in adult male and female offspring and an increased mechanical allodynia threshold in males. Analyses of gene expression within the hypothalamus-chosen for its involvement in the sex-specific pathogenesis of schizophrenia and the stress response-revealed significantly higher levels of the stress-sensitive genes and . Deleterious TE expression is often a hallmark of neuropsychiatric disease and we found sex-specific increases in the expression of several TEs including IAP, B2 SINE, and LINE-1 ORF1. The data from this study warrant the future consideration of chromatin stability and TEs as part of the mechanism that drives MIA-associated changes in the brain and behavior.
PubMed: 37139465
DOI: 10.1016/j.ynstr.2023.100538