Elevated ammonia cues hatching in red-eyed treefrogs: A mechanism for escape from drying eggs.

Egg dehydration can kill terrestrial frog embryos, and this threat is increasing with climate change and deforestation. In several lineages that independently evolved terrestrial eggs, and retained aquatic tadpoles, embryos accelerate hatching to escape from drying eggs, entering the water earlier and less developed. However, the cues that stimulate drying-induced early hatching are unknown. Ammonia is a toxic, water-soluble metabolic waste that accumulates within eggs as embryos develop and concentrates as eggs dehydrate. Thus, increasing ammonia concentration may be a direct threat to embryos in drying eggs. We hypothesized that it could serve as a cue, stimulating embryos to hatch and escape. The embryos of red-eyed treefrogs, Agalychnis callidryas, hatch early to escape from many threats, including dehydration, and are known to use mechanosensory, hypoxia, and light cues. To test if they also use high ammonia as a cue to hatch, we exposed stage-matched pairs of hatching-competent, well-hydrated sibling embryos to ammonia and control solutions in shallow water baths and recorded their behavior. Control embryos remained unhatched while ammonia-exposed embryos showed a rapid, strong hatching response; 95% hatched, on average in under 15 min. This demonstrates that elevated ammonia can serve as a hatching cue for A. callidryas embryos. This finding is a key step in understanding the mechanisms that enable terrestrial frog embryos to escape from egg drying, opening new possibilities for integrative and comparative studies on this growing threat.

Neonicotinoid and sulfoximine pesticides differentially impair insect escape behavior and motion detection.

Insect nervous systems offer unique advantages for studying interactions between sensory systems and behavior, given their complexity with high tractability. By examining the neural coding of salient environmental stimuli and resulting behavioral output in the context of environmental stressors, we gain an understanding of the effects of these stressors on brain and behavior and provide insight into normal function. The implication of neonicotinoid (neonic) pesticides in contributing to declines of nontarget species, such as bees, has motivated the development of new compounds that can potentially mitigate putative resistance in target species and declines of nontarget species. We used a neuroethologic approach, including behavioral assays and multineuronal recording techniques, to investigate effects of imidacloprid (IMD) and the novel insecticide sulfoxaflor (SFX) on visual motion-detection circuits and related escape behavior in the tractable locust system. Despite similar LD50 values, IMD and SFX evoked different behavioral and physiological effects. IMD significantly attenuated collision avoidance behaviors and impaired responses of neural populations, including decreases in spontaneous firing and neural habituation. In contrast, SFX displayed no effect at a comparable sublethal dose. These results show that neonics affect population responses and habituation of a visual motion detection system. We propose that differences in the sublethal effects of SFX reflect a different mode of action than that of IMD. More broadly, we suggest that neuroethologic assays for comparative neurotoxicology are valuable tools for fully addressing current issues regarding the proximal effects of environmental toxicity in nontarget species.

Evidence that increased cholecystokinin (CCK) in the periaqueductal gray (PAG) facilitates changes in Resident-Intruder social interactions triggered by peripheral nerve injury.

Individual differences in the effects of a chronic neuropathic injury on social behaviours characterize both the human experience and pre-clinical animal models. The impacts of these changes to the well-being of the individual are often underappreciated. Earlier work from our laboratory using GeneChip® microarrays identified increased cholecystokinin (CCK) gene expression in the periaqueductal gray (PAG) of rats that showed persistent changes in social interactions during a Resident-Intruder encounter following sciatic nerve chronic constriction injury (CCI). In this study, we confirmed these gene regulation patterns using RT-PCR and identified the anatomical location of the CCK-mRNA as well as the translated CCK peptides in the midbrains of rats with a CCI. We found that rats with persistent CCI-induced changes in social behaviours had increased CCK-mRNA in neurons of the ventrolateral PAG and dorsal raphe nuclei, as well as increased CCK-8 peptide expression in terminal boutons located in the lateral and ventrolateral PAG. The functional significance of these changes was explored by microinjecting small volumes of CCK-8 into the PAG of uninjured rats and observing their Resident-Intruder social interactions. Disturbances to social interactions identical to those observed in CCI rats were evoked when injection sites were located in the rostral lateral and ventrolateral PAG. We suggest that CCI-induced changes in CCK expression in these PAG regions contributes to the disruptions to social behaviours experienced by a subset of individuals with neuropathic injury.

A Conformational Escape Reaction of HIV-1 against an Allosteric Integrase Inhibitor.

HIV-1 often acquires drug-resistant mutations in spite of the benefits of antiretroviral therapy (ART). HIV-1 integrase (IN) is essential for the concerted integration of HIV-1 DNA into the host genome. IN further contributes to HIV-1 RNA binding, which is required for HIV-1 maturation. Non-catalytic-site integrase inhibitors (NCINIs) have been developed as allosteric IN inhibitors, which perform anti-HIV-1 activity by a multimodal mode of action such as inhibition of the IN-lens epithelium-derived growth factor (LEDGF)/p75 interaction in the early stage and disruption of functional IN multimerization in the late stage of HIV-1 replication. Here, we show that IN undergoes an adaptable conformational change to escape from NCINIs. We observed that NCINI-resistant HIV-1 variants have accumulated 4 amino acid mutations by passage 26 (P26) in the IN-encoding region. We employed high-performance liquid chromatography (HPLC), thermal stability assays, and X-ray crystallographic analysis to show that some amino acid mutations affect the stability and/or dimerization interface of the IN catalytic core domains (CCDs), potentially resulting in the severely decreased multimerization of full-length IN proteins (IN undermultimerization). This undermultimerized IN via NCINI-related mutations was stabilized by HIV-1 RNA and restored to the same level as that of wild-type HIV-1 in viral particles. Recombinant HIV-1 clones with IN undermultimerization propagated similarly to wild-type HIV-1. Our study revealed that HIV-1 can eventually counteract NCINI-induced IN overmultimerization by IN undermultimerization as one of the escape mechanisms. Our findings provide information on the understanding of IN multimerization with or without HIV-1 RNA and may influence the development of anti-HIV-1 strategies.IMPORTANCE Understanding the mechanism of HIV-1 resistance to anti-HIV-1 drugs could lead to the development of novel drugs with increased efficiency, resulting in more effective ART. ART composed of more potent and long-acting anti-HIV-1 drugs can greatly improve drug adherence and also provide HIV-1 prevention such as preexposure prophylaxis. NCINIs with a multimodal mode of action exert potent anti-HIV-1 effects through IN overmultimerization during HIV-1 maturation. However, HIV-1 can acquire some mutations that cause IN undermultimerization to alleviate NCINI-induced IN overmultimerization. This undermultimerized IN was efficiently stabilized by HIV-1 RNA and restored to the same level as that of wild-type HIV-1. Our findings revealed that HIV-1 eventually acquires such a conformational escape reaction to overcome the unique NCINI actions. The investigation into drug-resistant mutations associated with HIV-1 protein multimerization may facilitate the elucidation of its molecular mechanism and functional multimerization, allowing us to develop more potent anti-HIV-1 drugs and unique treatment strategies.

Investigation of the effect of a modified fragment of neuropeptide Y on memory phases and extrapolation escape of animals.

The article presents a study of the effect of a modified fragment of neuropeptide Y (H-L-Ile-L-Asn-L-Leu-L-Nle-L-Ser- L-Arg-L-Asn-L-Arg-L-Tyr-NH2) named nonapeptide NP9 on the memory phases and extrapolation escape of animals. The study was performed in the passive avoidance test with intact animals, scopolamine-treated animals, and the extrapolation escape task. NP9 was investigated in the dose range of 0.04-0.4 mg/kg with a single intranasal administration. The comparison drug used peptide nootropic medicine Semax® (Met-Glu-His-Phe-Pro-Gly-Pro) at a dose of 0.1 mg/kg. Efficiency was assessed by the retention latency, the percentage of animals that have reached the learning criterion, the number of incomplete attempts to enter, the antiamnestic activity index calculated by Butlers formula, and the number of animals that successfully performed the extrapolation escape task. Peptide NP9 was superior to Semax® in most indicators. It demonstrated the ability to improve memorization due to its effect on I phase of memory and facilitated extinction of negative experiences when administered after a stress stimulus. NP9 also increased the cognitive ability of animals in the conditions an aversive environment in the extrapolation escape test. Thus, peptide NP9 is promising for a further study as a potential drug for the treatment of cognitive impairment and therapy of post-traumatic stress disorder.

Improvement effects of tanshinone on the impaired cognition and motor function in MCAO mice with ischemic penumbra.

This study aims to investigate the effects of tanshinone on improving the impaired cognition and motor function in MCAO model mice with ischemic penumbra. MWM test was carried out to evaluate the spatial learning and memory performance and the cognitive function of mice. The area of cerebral infarction was analyzed by immunohistochemistry. The TUNEL apoptosis detection kit was used to detect neuronal apoptosis. On the 25th day, the induction model group had lower body weight than the control group and the tanshinone treatment group; the induction model group had decreased walking deficiency and correct area escape times than the other two groups; while, tanshinone treatment group had higher movement distance, movement speed, periphery entry frequency, grooming rate, decreased center entry frequency, infarction area, apoptotic neuron number, latent escape time than induction model group; additionally, the control group had increased periphery and corner entry frequency, but decreased center entry frequency and latent escape time than the other two groups. Tanshinone can reduce neuronal damage in the ischemic penumbra after stroke, improve the integrity of white and gray matter, and restore connectivity in motor and cognitive functions, thereby supporting recovery from ischemic stroke.

Circuits That Mediate Expression of Signaled Active Avoidance Converge in the Pedunculopontine Tegmentum.

An innocuous sensory stimulus that reliably signals an upcoming aversive event can be conditioned to elicit locomotion to a safe location before the aversive outcome ensues. The neural circuits that mediate the expression of this signaled locomotor action, known as signaled active avoidance, have not been identified. While exploring sensorimotor midbrain circuits in mice of either sex, we found that excitation of GABAergic cells in the substantia nigra pars reticulata blocks signaled active avoidance by inhibiting cells in the pedunculopontine tegmental nucleus (PPT), not by inhibiting cells in the superior colliculus or thalamus. Direct inhibition of putative-glutamatergic PPT cells, excitation of GABAergic PPT cells, or excitation of GABAergic afferents in PPT, abolish signaled active avoidance. Conversely, excitation of putative-glutamatergic PPT cells, or inhibition of GABAergic PPT cells, can be tuned to drive avoidance responses. The PPT is an essential junction for the expression of signaled active avoidance gated by nigral and other synaptic afferents.SIGNIFICANCE STATEMENT When a harmful situation is signaled by a sensory stimulus (e.g., street light), subjects typically learn to respond with active or passive avoidance responses that circumvent the threat. During signaled active avoidance behavior, subjects move away to avoid a threat signaled by a preceding innocuous stimulus. We identified a part of the midbrain essential to process the signal and avoid the threat. Inhibition of neurons in this area eliminates avoidance responses to the signal but preserves escape responses caused by presentation of the threat. The results highlight an essential part of the neural circuits that mediate signaled active avoidance behavior.

Naringin provides neuroprotection in CCL2-induced cognition impairment by attenuating neuronal apoptosis in the hippocampus.

BACKGROUND: Chemokine C-C motif ligand 2 (CCL2) is one of the most widely recognised proinflammatory chemokines in cognitive disorders. Currently, CCL2-targeting drugs are extremely limited. Thus, this study aimed to explore the neuroprotection afforded by naringin in CCL2-induced cognitive impairment in rats. METHODS: Before the CCL2 intra-hippocampal injection, rats were treated with naringin for 3 consecutive days via intraperitoneal injection. Two days post-surgery, the Morris water maze (MWM) and novel object recognition (NORT) tests were performed to detect spatial learning and memory and object cognition, respectively. Nissl staining and dUTP nick-end labelling (TUNEL) staining were performed to assess histopathological changes in the hippocampus. Commercial kits were used to measure the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the relative mRNA expression of interleukin 1ß, (IL-1ß), interleukin 6 (IL-6), glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), phosphate-activated glutaminase (PAG), cysteine aspartic acid-specific protease 8 (caspase-8), cysteine aspartic acid-specific protease 3 (caspase-3), cell lymphoma/leukaemia-2 (Bcl-2), and Bcl-2 associated X protein (Bax). RESULTS: In the MWM, the average escape latency and average swimming distance were significantly reduced and the crossing times were increased in the naringin-treated groups, compared with the CCL2 group. The NORT results revealed that, compared with the CCL2 rats, the discrimination index in the naringin-treated rats increased significantly. Nissl and TUNEL staining revealed that naringin protected the structure and survival of the neurons in the CA1 zone of the hippocampus. In the naringin-treated groups, the SOD and GSH-Px activities were increased, whereas the MDA levels were decreased. Furthermore, in the naringin-treated groups, the relative mRNA expression of IL-1ß and IL-6 was significantly decreased; GLAST and GLT-1 mRNA expression levels were increased, whereas PAG was decreased. In the naringin-treated groups, the relative mRNA expression levels of caspase-8, caspase-3, and Bax were decreased, whereas that of Bcl-2 was increased. CONCLUSION: Collectively, these data indicated that naringin alleviated the CCL2-induced cognitive impairment. The underlying mechanisms could be associated with the inhibition of neuroinflammation, oxidative stress, apoptosis, and the regulation of glutamate metabolism.

The effect of sevoflurane on the spatial recall ability and expression of apolipoprotein E and ß amyloid in the hippocampus in rats.

This study aimed to observe the recent spatial recall ability and the changes of expression of hippocampal apolipoprotein E (ApoE) and amyloid ß protein (Aß) in adult rats after inhaling sevoflurane anesthetic drugs, and to analyze the mechanism of action. For this purpose, a total of 54 adult SD clean-grade rats were selected in this study and were randomly divided into the sevoflurane anesthesia group, carrier gas group and control group, 18 rats in each group. The rats in the carrier gas group were inhaled with 1 L/min of oxygen O2+1 L/min air mixed carrier gas for 2 h, and the rats in the sevoflurane anesthesia group were given 3.2%sevoflurane for 2 hours based on the carrier gas group, the control rats were naturally reared. Before the model was copied, the Morris water maze experiment was performed before the material was taken. Some rat brain tissues were extracted on the first day (T1), the third day (T3), and the seventh day (T7) after model replication. The immunohistochemistry was used to measure the mean optical density (MOD) value of APOE and Aß in hippocampal CA1, CA3 and DG regions. The indicators above at different time points of each group were compared and analyzed. Results showed that the number of crossing the original platform at each time point, the residence time of the original platform quadrant, the number of entering the original platform quadrant, and the percentage of the original platform quadrant residence time in the sevoflurane anesthesia group and the carrier gas group were compared, and there were no significant differences between two groups (P>0.05). Compared with the carrier gas group, the MOD values of APOE in the hippocampus at T1 and T3 time points in the sevoflurane anesthesia group were decreased (P<0.05), the MOD values of Aß in the hippocampus at the T7 time point were increased (P<0.05). It concluded that Inhalation of 3.2%sevoflurane has no obvious damage to the recent spatial recall ability of adult rats. Within 7 days after inhalation of 3.2% sevoflurane, it can inhibit hippocampus Aß deposition through down-regulating APOE expression level. The critical time point for hippocampal Aß increasing was 7 days after anesthesia.

The effect of the insecticide diazinon on the osmoregulation and the avoidance response of the white leg shrimp (Penaeus vannamei) is salinity dependent.

Diazinon is one of the insecticides that represent a high risk for Costa Rican estuarine environments due to its widespread use in pineapple plantations. In estuaries, organisms are frequently submitted to stress caused by natural factors (e.g., continuous changes in salinity levels) and, additionally, to stress due to contamination. Therefore, the driving question of this study was: will organisms be more susceptible to suffer the deleterious effects caused by diazinon because of the stress resulting from the salinity changes? The estuarine shrimp Penaeus vannamei was used as the model organism and two responses were measured: osmoregulation (the physiological effect after a forced and continuous 24 h-exposure) and avoidance [the behavioural effect after a short (3 h) non-forced, multi-compartmented exposure]. Juveniles were exposed to diazinon (0.1, 1, 10 and 100 µg/L) at three different salinities (10, 20 and 30). Disruption in the capacity to regulate the haemolymph osmotic pressure was observed at a salinity of 30 in individuals exposed to diazinon and methanol (used as vehicle). At that salinity, the ability of shrimps to detect and avoid the highest diazinon concentrations was impaired. P. vannamei juveniles inhabit environments with a high variation in salinity, but with an optimum osmotic point close to a salinity of 20; therefore, the higher the salinity, the greater the vulnerability of shrimps to the effects of diazinon. From an ecological point of view, this combined effect of salinity and contamination might also limit the spatial distribution of the organisms.

Neuroprotective Effect of Bean Phosphatidylserine on TMT-Induced Memory Deficits in a Rat Model.

BACKGROUND: Trimethyltin (TMT) is a potent neurotoxin affecting various regions of the central nervous system, including the neocortex, the cerebellum, and the hippocampus. Phosphatidylserine (PS) is a membrane phospholipid, which is vital to brain cells. We analyzed the neuroprotective effects of soybean-derived phosphatidylserine (Bean-PS) on cognitive function, changes in the central cholinergic systems, and neural activity in TMT-induced memory deficits in a rat model. METHODS: The rats were randomly divided into an untreated normal group, a TMT group (injected with TMT + vehicle), and a group injected with TMT + Bean-PS. The rats were treated with 10% hexane (TMT group) or TMT + Bean-PS (50 mg·kg-1, oral administration (p.o.)) daily for 21 days, following a single injection of TMT (8.0 mg/kg, intraperitoneally (i.p.)). The cognitive function of Bean-PS was assessed using the Morris water maze (MWM) test and a passive avoidance task (PAT). The expression of acetylcholine transferase (ChAT) and acetylcholinesterase (AchE) in the hippocampus was assessed via immunohistochemistry. A positron emission tomography (PET) scan was used to measure the glucose uptake in the rat brain. RESULTS: Treatment with Bean-PS enhanced memory function in the Morris water maze (MWM) test. Consistent with the behavioral results, treatment with Bean-PS diminished the damage to cholinergic cells in the hippocampus, in contrast to those of the TMT group. The TMT+Bean-PS group showed elevated glucose uptake in the frontal lobe of the rat brain. CONCLUSION: These results demonstrate that Bean-PS protects against TMT-induced learning and memory impairment. As such, Bean-PS represents a potential treatment for neurodegenerative disorders, such as Alzheimer's disease.

Different Nanomaterials for Soil Remediation Affect Avoidance Response and Toxicity Response in Earthworm (Eisenia fetida).

The application of nano-level passivating agents in the remediation of soil heavy metal pollution has received widespread attention, but its harm to soil animals should also be addressed. This study explored the effect of three nanomaterials-nanohydroxyapatite apatite (n-HAP), nano zeolite (n-zeolite), and nanometer iron oxide (n-Fe3O4), on catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) activity and malondialdehyde (MDA) content through filter paper contact test. The effects of nanomaterials spiked at 1.5%wt of soils on earthworm avoidance behavior were also be studied, and the crystallinity and surface charge of three nanomaterials were characterized. The results showed that the activities of CAT, SOD and POD and the content of MDA have been changed at different level. And earthworms have obvious avoidance behavior to the three kinds of nanomaterials. Therefore, nanomaterials do have adverse effects on earthworms, and their biological toxicity should be considered when selecting passivating agents for soil heavy metal pollution remediation.

Express yourself: Individuals with bold personalities exhibit increased behavioral sensitivity to dynamic herbicide exposure.

The majority of ecotoxicological studies performed measure average responses from individuals which do not account for the inter-individual variation in the responses of animals to environmental stimuli (i.e. the personality of individuals). Thus, these designs assume that all individuals will respond to contaminant exposure in a similar manner. Additionally, commonly used constant, static exposure regime designs neglect to recognize the spatial and temporal variation in contaminant plume structures as they move throughout fluid environments. The purpose of this study was to understand the effects of the structural characteristics (concentration, duration, and frequency) of temporally and spatially variant contaminant plumes on the personality of individuals. This experimental design aimed to construct a sensitive definition of exposure by connecting sublethal effects of toxicants and realistic exposure regimes. This study used escape response of Faxonius virilis crayfish from the predatory odor of Micropterus salmoides prior to and following exposure to the herbicide, atrazine. Atrazine was delivered in pulses to flow through exposure arenas for a total of 47 h while manipulating the concentration, frequency, and duration of the herbicide pulses. Escape response of crayfish prior to exposure was used to categorize animals into bold and shy personalities. The change in escape response was analyzed and resulted in a personality-dependent behavioral sensitivity to the polluted environment. Individuals classified as bold showed increased change in response to predatory odor relative to shy animals. Bold animals exhibited decreased activity after exposure where no change was presented in shy individuals. Shifts in individual behavior have impacts on the population level (e.g. resource acquisition/value; interspecies competition) and the ecosystem level (e.g. food web dynamics; trophic cascades). This study demonstrates the importance of sensitive measures in ecological risk assessment methods.

The Effects of Selenomethionine on the Escape Behaviours of Fathead Minnows.

Selenium (Se) is an essential micronutrient for animals and yet becomes toxic with only a small increase in concentration. Toxicological studies have reported various effects of Se on fishes, including developmental impacts and deformities of the musculature and sensory systems. This paper investigates the impact of sublethal concentrations of Se on the ability of the Fathead Minnow (Pimephales promelas) to perform escape responses, a routine behaviour important to predator-prey dynamics. Predation is among the strongest evolutionary driving forces in nature. Changes to this dynamic can have effects that cascade through the ecosystem. We used responses to mechanical and visual stimuli to determine the impact of environmentally relevant concentrations of dietary selenomethionine on the behaviour of minnows. Latency to respond to the stimulus and kinematic performance were assessed. Our results indicated that there was no significant effect of selenomethionine on either the visual response to a threat or burst swimming behaviours of the fast-start response in minnows. Levels of Se in tissues approached that of tissue-specific guidelines set by regulatory bodies across North America. This suggests that current regulations are adequately protecting this key component of predator avoidance in Fathead Minnows.

Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity.

BACKGROUND: Lead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA. We hypothesized increased QA production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity. METHODS: Two experimental paradigms were used. In experiment one, Wistar rat pups were exposed to Pb via their dams' drinking water from postnatal day 1 to 21. Control group was given regular water. In the second protocol, QA (9 mM) or normal saline (as Vehicle Control) was infused into right lateral ventricle of 21-day old rats for 7 days using osmotic pumps. Learning and memory were assessed by Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats. QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain by immunohistochemistry on postnatal days 45 and 60. Expression of various molecules involved in learning and memory was analyzed by Western blot. Means of control and experimental groups were compared with two-way repeated measure ANOVA (learning) and t test (all other variables). RESULTS: Pb exposure increased QA level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA-immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the hippocampus, compared to control rats. In separate experiments, QA infusion impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was increased, compared to vehicle infused rats. CONCLUSION: Putting together the results of the two experimental paradigms, we propose that increased QA production in response to Pb exposure is a novel mechanism of Pb-induced neurotoxicity.

σ1 receptor ligands control a switch between passive and active threat responses.

Humans and many animals show 'freezing' behavior in response to threatening stimuli. In humans, inappropriate threat responses are fundamental characteristics of several mental illnesses. To identify small molecules that modulate threat responses, we developed a high-throughput behavioral assay in zebrafish (Danio rerio) and evaluated 10,000 compounds for their effects on freezing behavior. We found three classes of compounds that switch the threat response from freezing to escape-like behavior. We then screened these for binding activity across 45 candidate targets. Using target profile clustering, we identified the sigma-1 (σ1) receptor as having a role in the mechanism of behavioral switching and confirmed that known σ1 ligands also disrupt freezing behavior. Furthermore, mutation of the gene encoding σ1 prevented the behavioral effect of escape-inducing compounds. One compound, which we call finazine, potently bound mammalian σ1 and altered threat-response behavior in mice. Thus, pharmacological and genetic interrogation of the freezing response revealed σ1 as a mediator of threat responses in vertebrates.

Differential effects of cholecystokinin (CCK-8) microinjection into the ventrolateral and dorsolateral periaqueductal gray on anxiety models in Wistar rats.

Cholecystokinin (CCK) is one of the main neurohormone peptide systems in the brain, and a major anxiogenic mediator. The periaqueductal gray (PAG) is a key midbrain structure for defensive behaviors, which could include anxiety, fear, or even panic. The CCK system has wide distribution in the PAG, where the dorsolateral region (DL) participates in active defensive behavior and the ventrolateral region (VL) in passive defensive behavior. The aim of this study was to assess the effect of CCK-8 microinjection into DL-PAG or VL-PAG on anxiety-like behavior through two tests: elevated plus maze (EPM) and defensive burying behavior (DBB). CCK-8 (0.5 and 1.0 µg/0.5 µL) presently microinjected into the DL-PAG produced an anxiogenic-like effect on the EPM evidenced by decreasing the time spent/number of entries in open arms compared to vehicle group. Additionally, the latency to burying decreased and burying time increased on the DBB test. Contrarily, CCK-8 microinjected into the VL-PAG resulted in greater open-arm time and more open-arm entries compared to the vehicle-microinjected group. The results on the DBB test confirmed an anxiolytic-like response of CCK-8 into the VL-PAG. In conclusion, CCK-8 microinjected into DL-PAG produced anxiety-like behavior on EPM, and for first time reported on DBB. Contrarily, CCK-8 microinjected into the VL-PAG reduced anxiety-like behavior also for first time reported using both behavioral models EPM and DBB.

A cross-modal effect of noise: the disappearance of the alarm reaction of a freshwater fish.

Anthropogenic noise pollution is recognized as a major global stressor of animals. While many studies have assessed the unimodal impacts of noise pollution with a focus on intraspecific acoustic communication, little is known about noise pollution on the perception of visual and chemical information. The 'distracted prey hypothesis' posits that processing noise interferes with processing other information in the brain. Here, we found evidence for such a cross-modal effect of noise on the antipredator behaviour of a freshwater prey fish, the fathead minnow, Pimephales promelas. In laboratory trials, exposure to noise from a motorboat caused the total absence of the classical fright reaction of minnows to conspecific alarm cues, whereas an ambient noise control had no such impact. In natural habitats, the impairment of such antipredator behaviour due to noise pollution could have major fitness consequences. We discuss how our findings translate to animal ecology and the need for future studies that target specific management decisions regarding noise pollution.

Adaptation of Defensive Strategies by the Pea Aphid Mediates Predation Risk from the Predatory Lady Beetle.

Within a species, individual animals adopt various defensive strategies to resist natural enemies, but the defensive strategies that are adopted in response to variations in predation risk are poorly understood. Here, we assessed consecutive foraging processes on cohorts of two biotypes (green and red) of the pea aphid, Acyrthosiphon pisum, by the predatory lady beetle Propylea japonica, to investigate the adaptive mechanism underlying the defensive strategy. We observed the behavioral responses of individuals (continue feeding or escape, i.e., walk away or drop off from initial feeding site), simultaneously quantified the amount of alarm pheromone, (E)-ß-farnesene (EßF) released from cohorts using gas chromatography-mass spectrometry (GC-MS), and recorded the foraging times of predators in intervals. The results indicated that: (1) the anti-predator responses differed markedly between biotypes and among the stages of the consecutive foraging processes. (2) Few green cohorts tended to release EßF during the first foraging; those that did released only a low dose that did not increase the number of escapes. However, the amount of EßF rose rapidly following the second foraging process, which caused an intense escape response. In contrast, more red cohorts released greater amounts of EßF, which caused more individuals to escape from their innate feeding sites during the first foraging. During the second foraging, more red individuals tended to escape without releasing EßF in greater quantities. (3) The foraging time was effectively shortened in each biotype cohort that adopted diverse defensive strategies. This study of the defensive strategies of the pea aphid may contribute to understanding the intraspecific differences in aphid defense mechanisms.

Effects of spontaneous recurrent seizures on cognitive function via modulation of SNAREs expression.

PURPOSE: To explore whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complexes are involved in cognitive dysfunction induced by spontaneous recurrent seizures (SRS). MATERIALS AND METHODS: An animal model of epilepsy was established by intraperitoneal injection of kainic acid (KA). Following the onset of SRS, the rats were divided into control group, KA-SRS group, KA+SRS group and KA+SRS+VAP group. Morris water maze and open field test were conducted to evaluate the cognitive function. Protein and mRNA levels of SNAREs complex were measured by Western-blot and RT-PCR, respectively. Besides, the Ca2+ concentration in the hippocampus was also detected. RESULTS: A delayed escape latency and a reduced number of platform crossings were found in the KA+SRS group. Meanwhile, a longer moving distance and time spent in central area were also observed during the open field test. Besides, the Ca2+ concentration in the hippocampus of the KA+SRS group was markedly increased. However, when compared with the KA+SRS group, all indices in the KA+SRS+VAP group were markedly improved. Moreover, the SNARE complexes in the hippocampus of the KA+SRS group were significantly increased when compared with both control group and KA+SRS+VAP group. CONCLUSIONS: Results of our study demonstrated that the cognitive dysfunction caused by SRS may be attributed to the modulation expression of SNARE complexes.