Startle Research Articles

Chronic short sleep duration lengthens reaction time, but the deficit is not associated with motor preparation.

The purpose of this study was to investigate the association between chronic sleep duration and reaction time performance and motor preparation during a simple reaction time task with a startling acoustic stimulus in adults. This cross-sectional study included self-reported short sleepers (n = 25, ≤ 6 hr per night) and adequate sleepers (n = 25, ≥ 7.5 hr per night) who performed a simple reaction time task requiring a targeted ballistic wrist extension in response to either a control-tone (80 dB) or a startling acoustic stimulus (120 dB). Outcome measures included reaction times for each stimulus (overall and for each trial block), lapses, and proportion of startle responses. Chronic short sleepers slept on average 5.7 hr per night in the previous month, which was 2.8 hr per night less than the adequate sleepers. Results revealed an interaction between sleep duration group and stimulus type; the short sleepers had significantly slower control-tone reaction times compared with adequate sleepers, but there was no significant difference in reaction time between groups for the startling acoustic stimulus. Further investigation showed that chronic short sleepers had significantly slower control-tone reaction times after two blocks of trials lasting about 5 min, until the end of the task. Lapses were not significantly different between groups. Chronic short sleep duration was associated with poorer performance; however, these reaction time deficits cannot be attributed to motor preparation, as startling acoustic stimulus reaction times were not different between sleep duration groups. While time-on-task performance decrements were associated with chronic sleep duration, alertness was not. Sleeping less than the recommended sleep duration on a regular basis is associated with poorer cognitive performance, which becomes evident after 5 min.

Inhibition of reactive oxygen species production accompanying alternatively activated microglia by risperidone in a mouse ketamine model of schizophrenia.

Recent studies have highlighted the potential involvement of reactive oxygen species (ROS) and microglia, a major source of ROS, in the pathophysiology of schizophrenia. In our study, we explored how the second-generation antipsychotic risperidone (RIS) affects ROS regulation and microglial activation in the hippocampus using a mouse ketamine (KET) model of schizophrenia. KET administration resulted in schizophrenia-like behaviors in male C57BL/6J mice, such as impaired prepulse inhibition (PPI) of the acoustic startle response and hyper-locomotion. These behaviors were mitigated by RIS. We found that the gene expression level of an enzyme responsible for ROS production (Nox2), which is primarily associated with activated microglia, was lower in KET/RIS-treated mice than in KET-treated mice. Conversely, the levels of antioxidant enzymes (Ho-1 and Gclc) were higher in KET/RIS-treated mice. The microglial density in the hippocampus was increased in KET-treated mice, which was counteracted by RIS. Hierarchical cluster analysis revealed three morphological subtypes of microglia. In control mice, most microglia were resting-ramified (type I, 89.7%). KET administration shifted the microglial composition to moderately ramified (type II, 44.4%) and hyper-ramified (type III, 25.0%). In KET/RIS-treated mice, type II decreased to 32.0%, while type III increased to 34.0%. An invitro ROS assay showed that KET increased ROS production in dissociated hippocampal microglia, and this effect was mitigated by RIS. Furthermore, we discovered that a NOX2 inhibitor could counteract KET-induced behavioral deficits. These findings suggest that pharmacological inhibition of ROS production by RIS may play a crucial role in ameliorating schizophrenia-related symptoms. Moreover, modulating microglial activation to regulate ROS production has emerged as a novel avenue for developing innovative treatments for schizophrenia.

The behavioral and neurobiological response to sound stress in salmon.

Noise associated with human activities in aquatic environments can affect the physiology and behavior of aquatic species which may have consequences at the population and ecosystem levels. Low frequency sound is particularly stressful for fish, since it is an important factor in predator-prey interactions. Even though behavioral and physiological studies have been conducted to assess the effects of sound on fish species, neurobiological studies are still lacking. In this study we exposed farmed salmon to low frequency sound for 5 minutes a day for 30 trials and conducted behavioral observations and tissue sampling before sound exposure (timepoint zero; T0) and after 1 (T1), 10 (T2), 20 (T3) and 30 (T4) exposures, to assess markers of stress. These included plasma cortisol, neuronal activity, monoaminergic signaling, and gene expression in 4 areas of the forebrain. We found that sound exposure induced an activation of the stress response by eliciting an initial startle behavioral response, together with increased plasma cortisol levels and a decrease in neuronal activity in the hypothalamic tubercular nuclei (TN). At T3 and T4 salmon showed a degree of habituation in their behavioral and cortisol response. However, at T4, salmon showed signs of chronic stress with increased serotonergic activity levels in the dorsolateral and dorsomedial pallium, the preoptic area, and the TN, as well as an inhibition of growth and reproduction transcripts in the TN. Together, our results suggest that prolonged exposure to sound results in chronic stress that leads to neurological changes which suggest a reduction of life fitness traits.

A Computational Model for the Simulation of Prepulse Inhibition and Its Modulation by Cortical and Subcortical Units.

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.

The entactogen 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) as a treatment aid in psychotherapy and its safety concerns.

The phenylethylamine, 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'), is the prototypical example of an entactogen. Its original placement in highly restrictive drug usage categories in the US and UK, led to an inevitable restriction on MDMA neuroscience research and treatment. The dominant pharmacological effects of MDMA are its properties of release and inhibition of reuptake of amine neurotransmitter transporters for dopamine, norepinephrine, and serotonin. MDMA is an agonist of a wide range of receptors; its mood-altering effects are mediated via 5-HT2A receptors; this receptor may also mediate its effects on body temperature, analgesia, and anxiolytic properties. The mechanisms underlying MDMA's entactogenic properties of sociability and interpersonal closeness are not known but release and involvement of oxytocin, a peptide thought by some to be involved in social bonding, has been suggested. Adverse effects of MDMA are mostly transient; acute multiorgan adverse effects occurring during raves or crowded dance gatherings include dehydration, hyperthermia, seizures, rhabdomyolysis, disseminated intravascular coagulation, and acute renal failure. Deaths following MDMA taken by itself are rare compared to fatalities following coadministration with other drugs. A recent FDA-approved phase 3 clinical trial of MDMA for post-traumatic stress disorder (PTSD) led to the conclusion that MDMA-assisted therapy represents a potential breakthrough treatment meriting expedited clinical evaluation. Despite the ongoing deliberations by the FDA and EMA for approval of MDMA treatment of PTSD, the Australian Therapeutic Goods Administration (TGA) recently announced that after an evaluation of the therapeutic value, benefits, and risks of MDMA, it will permit its prescribing for the treatment of PTSD. Further examples of regulatory relaxation toward MDMA-assisted psychotherapy are underway. These include the FDA's recently approved clinical trial to assess MDMA's efficacy in the treatment of "asociality" in patients with schizophrenia and an open trial of MDMA treatment for alcohol-use disorder which showed decreased alcohol consumption. There are also ongoing studies on the little understood startle response, anxiety associated with life-threatening illness, and social anxiety in autistic adults.

Intermittent theta-burst stimulation to the right dorsolateral prefrontal cortex may increase potentiated startle in healthy individuals

Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.

Larval Zebrafish Startle Response Is Highly Sensitive to Crude Oil Exposure

Larval Zebrafish Startle Response Is Highly Sensitive to Crude Oil Exposure

A threat from within: Learning to fear by observing aversive bodily symptoms in others

Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily symptoms remain scarce. Therefore, the aim of the present study was to investigate whether fear in response to bodily symptoms can be acquired simply by observing a fearful reaction to provocation of aversive bodily symptoms in others. Forty healthy participants underwent an observational fear conditioning paradigm consisting of two phases. In the first phase, participants observed a demonstrator reacting to an aversive bodily symptom provocation (unconditioned stimulus or US, i.e., labored breathing) paired with one conditioned stimulus (CS+) but not with the other one (CS-, both CSs were geometric symbols presented on a screen the demonstrator was watching). In the second phase, participants were directly presented with the same conditioned stimuli, but in the absence of the US. Our results revealed enhanced conditioned fear responses in the beginning of the second phase to the CS + as compared to CS-, as indexed by greater skin conductance and subjective fear responses, as well as greater potentiation of startle eyeblink responses to the CS + as compared to the ITI. Taken together, these findings implicate that fear of bodily symptoms can be learned through observation of others, that is, without first-hand experience of bodily threat.

Reduced amplitude and slowed latency of the acoustic startle response in adolescents and adults with 22q11.2 deletion syndrome

Background22q11.2 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. MethodsStartle 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. ResultsAcross 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. ConclusionsReduced 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.

Down to size: Exploring the influence of plastic particle Dimensions on physiological and nervous responses in early-stage zebrafish

The chorion is the first protective barrier set to prevent numerous pollutants from damaging the developing embryo. However, depending on their size, some nanoplastics (NPs) can pass through this barrier and reach the embryo, while all microplastics (MPs) remain on the outside. This study brings a straight approach to compare MPs and NPs, and assess their direct and indirect effects on zebrafish embryos and larvae. Zebrafish eggs were exposed before 2 h post fertilization (hpf) to polystyrene MPs (5 μm) and NPs (250 nm) at a concentration of 1000 μg/L until 96 hpf. Physiotoxicity and neurotoxicity were assessed prior and post-hatching through several biomarkers. Response to hypoxia (upregulation of hif-1aa and hif-1ab) were found in embryos exposed to MPs, and partly found in those exposed to NPs. Embryos exposed to NPs showed significant tachycardia, reduced O2 consumption and increased apoptosis in the eyes, whereas MPs affected the expressions of all genes related to the neurodevelopment of embryos (elavl3, pax2a, pax6a, act1b). Post-hatching, physiological responses were muted. MPs and NPs exposures ended by evaluating larval behaviours during dark-and-light cycles. Both sizes of plastic particles negatively affected the visual motor response (VMR) and vibrational startle response (VSR). Thigmotaxis levels were significantly increased by NPs whereas MPs showed anxiolytic properties. This study shows that both MPs and NPs affect the physiology and neurodevelopment of zebrafish at different levels, before and after hatching.

Stressing out! Effects of acute stress on prepulse inhibition and working memory.

Prepulse inhibition (PPI) of the startle reflex serves as a pre-cognitive marker of sensorimotor gating, and its deficit may predict cognitive impairments. Startle reflex is modulated by many factors. Among them, stress has been a topic of interest, but its effects on both pre-cognitive and cognitive variables continue to yield divergent results. This study aims to analyze the effect of acute stress on PPI of the startle reflex and cognitive function (working memory, attention, inhibition, and verbal fluency). Participants were exposed to the MAST stress induction protocol or a stress-neutral task: stress group (n = 54) or control group (n = 54). Following stress induction, participants' startle responses were recorded, and cognition was assessed. The results revealed that participants in the stress group exhibited greater startle magnitude, lower PPI, and lower scores in working memory tests compared with the control group. Additionally, a correlation was found between working memory and PPI across all the participants, independent of stress group. These findings support the notion that after stress, both greater startle magnitude and diminished PPI could play an adaptive role by allowing for increased processing of stimuli potentially dangerous and stress-related. Similarly, our results lend support to the hypothesis that lower PPI may be predictive of cognitive impairment. Considering the impact of stress on both pre-cognitive (PPI) and cognitive (working memory) variables, we discuss the possibility that the effect of stress on PPI occurs through motivational priming and emphasize the relevance of considering stress in both basic and translational science.

359. Navigating Uncertainty: The Relationship Between Intolerance of Uncertainty and Startle Response in Adolescents With Trauma Exposure

359. Navigating Uncertainty: The Relationship Between Intolerance of Uncertainty and Startle Response in Adolescents With Trauma Exposure

Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence.

Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to stress-induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses. We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma. Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle). This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Identification of a Locus Coeruleus-amygdala Angiotensinergic Circuit: Implications for Stress-related Cardiovascular Diseases

Background: The locus coeruleus (LC) is a significant noradrenergic nucleus in the brain sensitive to afferent interoceptive signals. It responds to behavioral challenges by increasing noradrenaline release through ascending projections to the hypothalamus, thalamus, cortex, and amygdala. The brain renin-angiotensin system (RAS) plays a role in stress-related cardiovascular diseases, and previous research has identified angiotensin II (Ang II) and its receptors in the LC. The current study aimed to gain a deeper understanding of the function of the Ang II type 1 receptor (AT1R) in the LC, particularly its involvement in transmitting interoceptive cardiovascular signals by regulating LC activity. Methods: Using AT1R-eGFP and AT1R-Cre mice combined with neuroanatomical tract-tracing, chemogenetic and behavioral approaches, we examined AT1R expressing neurons in the LC. Dual immunohistochemistry was used in AT1R-eGFP reporter mice to characterize LC-AT1R-eGFP+ cells by looking at the colocalization of noradrenergic neuron maker tyrosine hydroxylase (TH) and GFP. Cre-inducible tracing with AT1R-cre mice was applied for circuit anterograde analysis and in vivo chemogenetics were used for behavior testing and analysis. Results: The majority of AT1R-eGFP+ neurons (94%) in the LC were found to be co-localized with TH. By using anterograde labeling with cre-inducible GFP virus (AAV-DIO-GFP) in AT1R-Cre mice, it was revealed that the AT1R+ neurons in the LC predominantly project to the amygdala and extended amygdala regions. Only a few or no projections to other brain areas known to receive LC inputs were observed. Within the amygdala, the AT1R+ nerve terminals were specifically limited to the medial division of the central amygdala (CeM) and the basomedial amygdala (BMA). Subsequently, AT1R was deleted from LC by injecting Cre virus into AT1R-Flox mice. Although the general anxiety level remained unchanged, restraint stress-induced anxiety was attenuated following LC AT1R deletion as shown by increased open arm distance in the elevated plus maze (EPM) test (21.7±6.6mm AAV-GFP vs. 98.1±27.5mm AAV-Cre, p<0.05, n=10). Moreover, the study employed Cre-dependent inhibitory and excitatory designer receptors exclusively activated by designer drug (hM4Di and hM3Dq DREADD) with Clozapine-n-oxide (CNO) to selectively silence and activate the AT1R+ neurons in the LC. The inhibition of AT1R+ neurons decreased the baseline anxiety level in mice (36.6±8.6mm Saline vs. 153.4±38.9mm CNO, p<0.01, n=8, EPM open arm distance), while activation of AT1R+ neurons increased baseline anxiety level (963.1±223.1mm Saline vs. 408.5±92mm CNO, p<0.01, n=10, EPM open arm distance). Additionally, the acoustic startle response, which is associated with anxiety levels, was reduced after silencing the LC AT1R+ neurons (324±39.2mV Saline vs. 168.8±54.1mV CNO, p<0.05, n=8). Conclusion: These findings suggest that a specific group of angiotensinergic LC neurons sends projections to the amygdala, highlighting the potential significance of AT1R in mediating noradrenergic activation between the LC and amygdala. Future investigations will explore the response of LC AT1R+ neurons to stress-induced cardiovascular stimuli and afferent interoceptive LC inputs, which may offer novel insights, and new therapeutic direction for the link between stress disorders and cardiovascular disease risk. NIH 1R01HL137103-01A1. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Novel Animal Behavioral Model For Assessing Arousal and Anxiety States: Implications for Post-Traumatic Stress Disorder

Background: Post-traumatic stress disorder (PTSD) is a highly prevalent disorder with widespread impact on health co-morbidities, including cardiovascular disease (CVD). There is a pressing need to understand its underlying mechanisms. This study builds upon our previous published clinical and pre-clinical findings assessing cardiovascular and autonomic responses to stress. Using a recently developed behavioral model and lab-developed software for integrated behavioral and cardio-autonomic analysis, we sought to assess the impact of chronic unpredictable threat reminders on arousal and anxiety behavior as well as cardiovascular and autonomic function in pair-housed mice. Methods: Male and female C57bl/6J mice underwent Pavlovian auditory fear conditioning (n=10-16/group) and were returned to the home cage, equipped with speaker and top-down camera with infrared capabilities. Using a customized software to remotely deliver the conditioned stimulus (CS), pair-housed mice received 6 tones (30sec. 6kHz) throughout the light-dark (LD) cycle over a 24hr period (3 light, 3 dark), repeated for 14 days. The first CS during each LD cycle was recorded and freezing behavior was manually scored. Videos were used to train DeepLabCutTM (DLC) for automated behavioral analysis. On day 15, to evaluate whether evoked freezing is context-dependent, mice were placed into a novel context and CS-dependent freezing was measured. Mice then underwent elevated plus maze (EPM), uncued startle reactivity testing, and fear-potentiated startle (FPS) to assess locomotor, anxiety, and hyperarousal and heightened vigilant behaviors. Results: Following 14 days of chronic unpredictable conditioned threat reminders, fear-conditioned male and female mice exhibited strong CS-evoked freezing in the home cage. Circadian evaluation revealed enhanced freezing in the light versus the dark phase ( males, p<0.01; females, p<0.01). DLC analysis successfully and accurately quantified freezing of group-housed mice. Over 14 days, CS-dependent freezing declined, though this was context-dependent as freezing was significantly higher in a novel context on day 15 ( males, p<0.01; females, p=0.02). While chronic threat reminders did not affect behavior in the EPM, males, but not females, displayed hyperarousal in both uncued (startle to 120dB, males, p<0.01, females, p=0.62) and cued (FPS, males, p=0.04, females, p=0.60) startle testing, though neither males nor females had increased background anxiety during FPS ( males, p=0.77, females, p=0.77). Conclusions: Here we demonstrate, using lab-developed software, environment- and circadian-dependent conditioned freezing in the home cage of group-housed mice. These results further demonstrate that the delivery of chronic intermittent unpredictable conditioned threat reminders leads to an enhanced startle phenotype, that may be sex-dependent. Future studies are needed to assess direct measures of autonomic function in this model, which could provide novel insights into and potentially revealing new therapeutic and preventive strategies for mitigating PTSD-related autonomic dysfunction. (CDMRP) PR210574. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Age-Related Changes in Survival Behaviour in Parasite-Free Hatchery-Reared Rainbow Trout (Oncorhynchus mykiss).

Millions of hatchery-reared Rainbow trout are currently released in Australian waters to support recreational fisheries objectives, yet many of these fish die soon after release. In addition, little is known whether these fish harbour parasites that can potentially threaten freshwater ecosystems and human health. Here, we tested the behaviour of hatchery-reared trout using six tank-based tests at six different ages to evaluate their chances of survival and then dissected fish to investigate parasite prevalence. At 7 weeks of age fish readily emerged from a hide and showed the greatest number of startle responses to predators. Behaviour around 25-29 weeks of age was relatively "shy", staying in shelter and avoiding open water. At around 37-41 weeks of age though, behaviour changed, with fish emerging from a hide more readily and exploring the environment. Interestingly, at 58 weeks of age fish were slower to initiate exploration, possibly indicating a return to "shyer" behaviour. All fish underwent thorough parasite examination, revealing no infections. We conclude that knowledge of the behaviour of hatchery-reared fish at different ages is useful for decisions around the timing of release that balance the needs of recreational fishers whilst managing the impact on freshwater ecosystem.

Non-Conscious Affective Processing in Asset Managers during Financial Decisions: A Neurobiological Perspective

In the world of finance, considerable attention is given to improving machine learning techniques to predict the future of stock markets. However, for obvious reasons, this turns out to be an unsolvable mission, most likely because the real world is not driven by algorithms but by human beings. In response to this, the present study has its focus on raw affective responses in actual asset managers during their decision making regarding controlled financial scenarios. Nineteen asset managers were invited and asked to make sell/buy decisions related to visual presentations of three different price developments of different assets. The three scenarios were “crash”, “stable” and “gain”. Parallel to their decision making, startle reflex modulation (SRM) was used to measure non-conscious affective responses without demanding any respective explicit responses (no conscious language processing involved). Interestingly, two further factors were introduced. First, all participants had to make their decisions once while being informed that 0% prior investments (low exposure) have been made into the presented assets, and once being informed that a large investment consisting of 25% of ones’ overall portfolio has been made prior to making the decision (high exposure). Second, the factor experience was included dividing all participants into two groups, one with low experience and the other with high experience. First, across both these extra factors, it was found that “crash” scenarios resulted in the most negative affective responses. The most positive affective responses were found for “gain” scenarios, while the “stable” condition was in between. Interestingly, the factor of prior investment (i.e., exposure) had an effect. Non-conscious affective responses during decision making related to the “stable” condition varied as a function of “exposure”. In the low exposure condition, affective responses to decision making during the “stable” scenario were most negative, even more negative than in “crash” scenarios. The factor experience also had an effect, but due to the small sample size, no significant interaction occurred. However, t-tests revealed the same significant effects in the experienced group as found in the 0% prior investment condition. To our knowledge, this is the first empirical investigation measuring non-conscious affective responses during decision making in the context of asset management. Thus, this study might form an interesting basis for new strategies to explore non-conscious human brain functions instead of inventing new algorithms to make asset management more successful.

Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB

BackgroundMucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in the MPS IIIB mouse model as well as examine clinically-relevant behavioral domains not yet explored in this model.MethodsUsing the MPS IIIB mouse model, we explored early developmental trajectories of communication and gait, and later social behavior, fear-related startle and conditioning, and visual capabilities. In addition, we examined brain structure and function via magnetic resonance imaging and diffusion tensor imaging.ResultsWe observed reduced maternal isolation-induced ultrasonic vocalizations in MPS IIIB mice relative to controls, as well as disruption in a number of the spectrotemporal features. MPS IIIB also exhibited disrupted thermoregulation during the first two postnatal weeks without any differences in body weight. The developmental trajectories of gait were largely normal. In early adulthood, we observed intact visual acuity and sociability yet a more submissive phenotype, increased aggressive behavior, and decreased social sniffing relative to controls. MPS IIIB mice showed greater inhibition of startle in response to a pretone with a decrease in overall startle response and reduced cued fear memory. MPS IIIB also weighed significantly more than controls throughout adulthood and showed larger whole brain volumes and normalized regional volumes with intact tissue integrity as measured with magnetic resonance and diffusion tensor imaging, respectively.ConclusionsTogether, these results indicate disease markers are present as early as the first two weeks postnatal in this model. Further, this model recapitulates social, sensory and fear-related clinical features. Our study using a mouse model of MPS IIIB provides essential baseline information that will be useful in future evaluations of potential treatments.

Unpredictable Mixed-Valence Outcomes Induce a Chronic and Reversible Generalized Anxiety-like Phenotype in Male Mice

BackgroundClinical anxiety is a generalized state characterized by feelings of apprehensive expectation and is distinct from momentary responses such as fear or stress. In contrast, most laboratory tests of anxiety focus on acute responses to momentary stressors. MethodsApprehensive expectation was induced by subjecting mice (for 18 days) to manipulations in which a running response (experiment 1) or a conditioned stimulus (experiment 2) were unpredictably paired with reward (food) or punishment (footshock). Before this treatment, the mice were tested in an open field and light/dark box to assess momentary responses that are asserted to reflect state anxiety. After treatment, the mice were assessed for state anxiety in an elevated plus maze, social interaction test, startle response test, intrusive object burying test, and stress-induced corticosterone elevations. In experiment 3, we treated mice similarly to experiment 1, but after mixed-valence training, some mice received either no additional training, additional mixed-valence training, or were shifted to consistent (predictable) reinforcement with food. ResultsWe consistently observed an increase in anxiety-like behaviors after the experience with mixed-valence unpredictable reinforcement. This generalized anxiety persisted for at least 4 weeks after the mixed-valence training and could be reversed if the mixed-valence training was followed by predictable reinforcement with food. ConclusionsResults indicate that experience with unpredictable reward/punishment can induce a chronic state analogous to generalized anxiety that can be mitigated by exposure to stable, predictable conditions. This learned apprehension protocol provides a conceptually valid model for the study of the etiology and treatment of anxiety in laboratory animals.