Consistency in Reporting of Loss of Righting Reflex for Assessment of General Anesthesia in Rats and Mice: A Systematic Review.

General anesthesia induces a reversible loss of consciousness (LOC), a state that is characterized by the inability to feel pain. Identifying LOC in animals poses unique challenges, because the method most commonly used in humans, responding to questions, cannot be used in animals. For over a century, loss of righting reflex (LORR) has been used to assess LOC in animals. This is the only animal method that correlates directly with LOC in humans and has become the standard proxy measure used in research. However, the reporting of how LORR is assessed varies extensively. This systematic literature review examined the consistency and completeness of LORR methods used in rats and mice. The terms 'righting reflex,' 'anesthesia,' 'conscious,' 'rats,' 'mice,' and their derivatives were used to search 5 electronic databases. The abstracts of the 985 articles identified were screened for indications that the study assessed LORR in mice or rats. Full texts of selected articles were reviewed for LORR methodological completeness, with reported methods categorized by 1) animal placement method, 2) behavioral presence of righting reflex, 3) duration of LORR testing, 4) behavioral LORR, and 5) animal position for testing LORR. Only 22 papers reported on all 5 methodological categories. Of the 22 papers, 21 used unique LORR methodologies, with descriptions of LORR methods differing in at least one category as compared with all other studies. This variability indicates that even papers that included all 5 categories still had substantial differences in their methodological descriptions. These findings reveal substantial inconsistencies in LORR methodology and reporting in the biomedical literature likely compromising study replicability and data interpretation.

Low-frequency noise impairs righting reflex behavior by disrupting central nervous system in the sea slug Onchidium reevesii.

Anthropogenic noise has significantly increased due to human activities, posing a threat to the health and survival of marine organisms. However, current studies have often emphasized its effects on the physiological aspects of marine organisms, while ignored the relationship between the neuroendocrine system and behavior. This study aimed to evaluate the righting behavior and relevant physiological functions of the central nervous system (CNS) in sea slug (Onchidium reevesii) exposed to low-frequency noise and subsequent noise removal. The duration of the sea slugs' righting reflex increased with longer noise exposure time. The degree of neuronal cell damage and apoptosis were significantly increased and relevant gene expressions were affected (Glu, AChE, FMRFamide and CaMKII) (P < 0.05). After the removal of noise, the righting reflex speed gradually recovered, and the degree of neuronal cell damage, apoptosis and the expression levels of genes continued to decrease. Pearson correlation analysis showed that the righting time was positively correlated with CNS tissue and DNA damage, apoptosis rate, and negatively correlated with the expression levels of genes. Therefore, low-frequency noise exposure causes damage to the CNS of sea slugs, subsequently impairing their normal behavior. Sea slugs exhibited partial recovery within 384 h after removing noise. These findings provide valuable insights into the effects of low-frequency noise on the CNS and behavior of marine invertebrates.

Use of Loss of Righting Reflex to Assess Susceptibility to Carbon Dioxide Gas in Three Mouse Strains.

Exposure to CO2 gas is a common rodent euthanasia method. CO2 activates nociceptors in rats and is painful to humans at concentrations equal to or greater than 32.5% The concentration of CO2 at which rodents become unconsciousness is inadequately defined. We used loss of righting reflex (LORR) to identify the concentration at which CO2 caused loss of consciousness in C57Bl/6, CD1 and 129P3J mice (16 females and 16 males per strain). We used a custom built, rotating, motorized cylinder to determine LORR as CO2 concentrations were increased. Two LORR assessment methods were used: 1) a 1-Paw assessment in which the righting reflex was considered to be present if one or more paws contacted the cylinder after rotation into dorsal recumbency and 2) a 4-Paw assessment in which the righting reflex was considered to be present only if all 4 paws contacted the cylinder. LORR test data were analyzed with Probit regression and dose response curves were plotted. 1-Paw EC95 values (CO2 concentration at which LORR occurred for 95% of the population) were: C57Bl/6; 30.7%, CD1; 26.2%, 129P3J; 20.1%. The EC95 for C57Bl/6 was significantly higher than that of the 129P3J mice, with no significant differences between other strains. Four-Paw EC95 values were: C57Bl/6; 22.8%, CD1; 25.3%, 129P3J; 20.1%. Values for 129P3J mice were significantly lower than those of CD1 mice), with no significant difference between other strains. The EC95 varied significantly between 1-Paw and 4-Paw methods only for C57Bl/6 mice. These results suggest a potential for nociception and pain to occur in some individuals of some mouse strains during CO2 euthanasia.

Effect of electromagnetic fields from renewable energy subsea power cables on righting reflex and physiological response of coastal invertebrates.

Offshore renewables are expanding, yet more information is required to understand their possible impacts on the environment. Little is known about the effects of Electromagnetic Fields (EMF) from subsea power cables on marine life. This study simulated an EMF of 500 µT, as modelled for an export cable over a rocky shore, where the industry standard cable burial would not be possible. Righting reflex, refractive index of haemolymph/coelomic fluid, and total haemocyte/coelomocyte counts were measured for four coastal invertebrates (Asterias rubens, Echinus esculentus, Necora puber, and Littorina littorea). No significant differences were found in either behavioural or physiological responses. This was the first study to investigate EMF exposure on righting reflex, and the first ever EMF study on edible sea urchins and periwinkles, and only one of a couple for common starfish and velvet crabs. It therefore, provides valuable data for environmental impact assessments, marine spatial planning, and commercial fisheries.

Glycyrrhizae Radix suppresses lipopolysaccharide- and diazepam-induced nerve inflammation in the hippocampus, and contracts the duration of pentobarbital- induced loss of righting reflex in a mouse model.

Nerve inflammation is linked to the development of various neurological disorders. This study aimed to examine whether Glycyrrhizae Radix effectively influences the duration of the pentobarbital-induced loss of righting reflex, which may increase in a mouse model of lipopolysaccharide (LPS)-induced nerve inflammation and diazepam-induced γ-aminobutyric acid receptor hypersensitivity. Furthermore, we examined the anti-inflammatory effects of Glycyrrhizae Radix extract on LPS-stimulated BV2 microglial cells, in vitro. Treatment with Glycyrrhizae Radix significantly decreased the duration of pentobarbital-induced loss of righting reflex in the mouse model. Furthermore, treatment with Glycyrrhizae Radix significantly attenuated the LPS-induced increases in interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha at the mRNA level, and it significantly reduced the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus 24 h after LPS treatment. Treatment with Glycyrrhizae Radix also suppressed the release of nitric oxide, interleukin-1ß, interleukin-6, and tumor necrosis factor protein in culture supernatants of LPS-stimulated BV2 cells. In addition, glycyrrhizic acid and liquiritin, active ingredients of Glycyrrhizae Radix extract, reduced the duration of pentobarbital-induced loss of righting reflex. These findings suggest that Glycyrrhizae Radix, as well as its active ingredients, glycyrrhizic acid and liquiritin, may be effective therapeutic agents for the treatment of nerve inflammation-induced neurological disorders.

Sensory fusion in the hoverfly righting reflex.

We study how falling hoverflies use sensory cues to trigger appropriate roll righting behavior. Before being released in a free fall, flies were placed upside-down with their legs contacting the substrate. The prior leg proprioceptive information about their initial orientation sufficed for the flies to right themselves properly. However, flies also use visual and antennal cues to recover faster and disambiguate sensory conflicts. Surprisingly, in one of the experimental conditions tested, hoverflies flew upside-down while still actively flapping their wings. In all the other conditions, flies were able to right themselves using two roll dynamics: fast ([Formula: see text]50ms) and slow ([Formula: see text]110ms) in the presence of consistent and conflicting cues, respectively. These findings suggest that a nonlinear sensory integration of the three types of sensory cues occurred. A ring attractor model was developed and discussed to account for this cue integration process.

Correlation between nystagmus intensity and vestibular-ocular reflex gain in benign paroxysmal positional vertigo: A prospective, clinical study.

BACKGROUND: Video head impulse test (vHIT) and videonystagmography (VNG) provide significant benefits in evaluating benign paroxysmal positional vertigo (BPPV) and determining the semicircular canal localization of the otoconia. OBJECTIVE: This study aimed to investigate the relationship between vestibular-ocular reflex (VOR) gains measured via vHIT and the slow-phase velocity (SPV) of nystagmus in patients with the posterior semicircular canal (PSCC)-BPPV. METHODS: Sixty-two patients were included in this study and divided into the study (n = 32, patients with isolated PSCC-BPPV) and control (n = 30, age- and sex-matched healthy individuals) groups. While VOR gains were measured with vHIT in both groups and compared between groups, the SPV values of nystagmus observed during the Dix-Hallpike maneuver in the study group were recorded using VNG and compared with the VOR gains of the study group. RESULTS: There were significant differences in posterior canal VOR gains between the study and control groups (p < 0.001 and p < 0.01, respectively). Although the affected PSCC had decreased VOR gains versus the control group, it was still within the normal range. However, there was no significant relationship between the VOR gains of the affected PSCC and the SPV of the nystagmus. CONCLUSIONS: vHIT can help detect semicircular canal dysfunction in patients with PSCC-BPPV. The SPV values of nystagmus on VNG during the Dix-Hallpike maneuver do not correlate with the level of VOR gain.

Metabolic gene signature in white adipose tissue of oral doses raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] that prevent diet-induced weight gain and induce loss of righting reflex.

Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a synthetic flavoring agent and dietary supplement for weight control. This study investigated the metabolic signature of oral doses of RK that prevent weight gain or promote loss of righting reflex (LORR) in C57Bl/6J mice. Daily RK 200 mg/kg prevented high-fat diet (HFD; 45% Kcal fat) fed weight gain (∼8% reduction) over 35 days. RNA-seq of inguinal white adipose tissue (WAT) performed in males revealed 12 differentially expressed genes. Apelin (Apln) and potassium voltage-gated channel subfamily C member (Kcnc3) expression were elevated with HFD and normalized with RK dosing, which was confirmed by qPCR. Acute RK 640 mg/kg produced a LORR with a <5 min onset with a >30 min duration. Acute RK 200 mg/kg increased gene expression of Apln, Kcnc3, and nuclear factor erythroid 2-related factor 2 (Nrf2), but reduced acetyl-COA carboxylase (Acc1) and NAD(P)H quinone dehydrogenase 1 (Nqo1) in inguinal WAT. Acute RK 640 mg/kg elevated interleukin 6 (Il 6) and heme oxygenase 1 (Hmox1) expression, but reduced Nrf2 in inguinal and epididymal WAT. Our findings suggest that RK has a dose-dependent metabolic signature in WAT associated with either weight control or LORR.

The impact of seismic survey exposure on the righting reflex and moult cycle of Southern Rock Lobster (Jasus edwardsii) puerulus larvae and juveniles.

Anthropogenic aquatic noise is recognised as an environmental pollutant with the potential to negatively affect marine organisms. Seismic surveys, used to explore subseafloor oil reserves, are a common source of aquatic noise that have garnered attention due to their intense low frequency inputs and their frequent spatial overlap with coastal fisheries. Commercially important Southern Rock Lobster (Jasus edwardsii) adults have previously shown sensitivity to signals from a single seismic air gun. Here, the sensitivity of J. edwardsii juveniles and puerulus to the signals of a full-scale seismic survey were evaluated to determine if early developmental stages were affected similarly to adults, and the range of impact. To quantify impact, lobster mortality rates, dorsoventral righting reflex and progression through moult cycle were evaluated following exposure. Exposure did not result in mortality in either developmental stage, however, air gun signals caused righting impairment to at least 500 m in lobsters sampled immediately following exposure, as had previously been reported in adults with corresponding sensory system damage following exposure. Impairment resulting from close range (0 m) exposure appeared to be persistent, as previously reported in adults, whereas juveniles exposed at a more distant range (500 m) showed recovery, indicating that exposure at a range of 500 m may not cause lasting impairment to righting. Intermoult duration was (time between moults) significantly increased in juveniles exposed at 0 m from the source, indicating the potential for slowed development, growth, and physiological stress. These results demonstrate that exposure to seismic air gun signals have the potential to negatively impact early life history stages of Southern Rock Lobsters. The similarity of both the impacts and the sound exposure levels observed here compared to previous exposure using a single air gun offer validation for the approach, which opens the potential for accessible field-based experimental work into the impact of seismic surveys on marine invertebrates.

Recovery mechanisms in the dragonfly righting reflex.

Insects have evolved sophisticated reflexes to right themselves in mid-air. Their recovery mechanisms involve complex interactions among the physical senses, muscles, body, and wings, and they must obey the laws of flight. We sought to understand the key mechanisms involved in dragonfly righting reflexes and to develop physics-based models for understanding the control strategies of flight maneuvers. Using kinematic analyses, physical modeling, and three-dimensional flight simulations, we found that a dragonfly uses left-right wing pitch asymmetry to roll its body 180 degrees to recover from falling upside down in ~200 milliseconds. Experiments of dragonflies with blocked vision further revealed that this rolling maneuver is initiated by their ocelli and compound eyes. These results suggest a pathway from the dragonfly's visual system to the muscles regulating wing pitch that underly the recovery. The methods developed here offer quantitative tools for inferring insects' internal actions from their acrobatics, and are applicable to a broad class of natural and robotic flying systems.

Yokukansan suppresses neuroinflammation in the hippocampus of mice and decreases the duration of lipopolysaccharide- and diazepam-mediated loss of righting reflex induced by pentobarbital.

Neuroinflammation is associated with the development of hypoactive delirium, which results in poor clinical outcomes. Drugs effective against hypoactive sur have not yet been established. Yokukansan has an anti-neuroinflammatory effect, making it potentially effective against hypoactive delirium. This study aimed to examine the effect of Yokukansan on the pentobarbital-induced loss of righting reflex duration extended with lipopolysaccharide (LPS)-induced neuroinflammation and diazepam-induced gamma-aminobutyric acid receptor stimulation in a mouse model. The active ingredients in Yokukansan and its anti-neuroinflammatory effect on the hippocampus were also investigated. Furthermore, we examined the in vitro anti-inflammatory effects of Yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Findings revealed that treatment with Yokukansan significantly decreased the duration of pentobarbital-induced loss of righting reflex by attenuating the LPS-induced increase in interleukin-6 and tumor necrosis factor-alpha levels in the hippocampus. Moreover, treatment with Yokukansan significantly decreased the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus after 24 h of LPS administration. In addition, glycyrrhizic acid, an active ingredient in Yokukansan, partially decreased the duration of pentobarbital-induced loss of righting reflex. Treatment with Yokukansan also suppressed the expression of inducible nitric oxide, interleukin-6, and tumor necrosis factor mRNA in LPS-stimulated BV2 cells. Thus, these findings suggest that Yokukansan and glycyrrhizic acid may be effective therapeutic agents for treating neuroinflammation-induced hypoactive delirium.

Disruption of self-motion perception without vestibular reflex alteration in ménière's disease.

BACKGROUND: Self-motion misperception has been observed in vestibular patients during asymmetric body oscillations. This misperception is correlated with the patient's vestibular discomfort. OBJECTIVE: To investigate whether or not self-motion misperception persists in post-ictal patients with Ménière's disease (MD). METHODS: Twenty-eight MD patients were investigated while in the post-ictal interval. Self-motion perception was studied by examining the displacement of a memorized visual target after sequences of opposite directed fast-slow asymmetric whole body rotations in the dark. The difference in target representation was analyzed and correlated with the Dizziness Handicap Inventory (DHI) score. The vestibulo-ocular reflex (VOR) and clinical tests for ocular reflex were also evaluated. RESULTS: All MD patients showed a noticeable difference in target representation after asymmetric rotation depending on the direction of the fast/slow rotations. This side difference suggests disruption of motion perception. The DHI score was correlated with the amount of motion misperception. In contrast, VOR and clinical trials were altered in only half of these patients. CONCLUSIONS: Asymmetric rotation reveals disruption of self-motion perception in MD patients during the post-ictal interval, even in the absence of ocular reflex impairment. Motion misperception may cause persistent vestibular discomfort in these patients.

Lateralized motor behaviour in the righting responses of the cane toad (Rhinella marina).

This paper reports a series of tests for fore- and hind-limb preferences used by cane toads, Rhinella marina, to assist returning to the righted position after being overturned. We confirm the strong and significant right-handedness reported in this species, which under certain conditions exceeded 90% right-hand preference at the group level. Toads were tested under a variety of conditions including horizontal and inclined surfaces, with and without the opportunity for the forelimbs to grasp a support, in order to assess the effects of different vestibular and proprioceptive input on the strength and direction of fore- and hind-limb preferences. A range of behavioural strategies indicated learning effects; however, the strength or direction of limb preferences did not increase significantly with experience, even in toads retested multiple times. Comparisons with the mammalian condition for limb preferences are discussed with relevance to practice effects and established limb preferences, and to effects associated with arousal or stress. In contrast to the expectation that handedness in toads represents intentional or voluntary preferences, the presence of lateralized central pattern generators in the toads is postulated to explain the different forms of lateralization revealed by our tests.

Hyper-SUMOylation of SMN induced by SENP2 deficiency decreases its stability and leads to spinal muscular atrophy-like pathology.

Spinal muscular atrophy (SMA), a degenerative motor neuron disease and a leading cause of infant mortality, is caused by loss of functional survival motor neuron (SMN) protein due to SMN1 gene mutation. Here, using mouse and cell models for behavioral and histological studies, we found that SENP2 (SUMO/sentrin-specific protease 2)-deficient mice developed a notable SMA-like pathology phenotype with significantly decreased muscle fibers and motor neurons. At the molecular level, SENP2 deficiency in mice did not affect transcription but decreased SMN protein levels by promoting the SUMOylation of SMN. SMN was modified by SUMO2 with the E3 PIAS2α and deconjugated by SENP2. SUMOylation of SMN accelerated its degradation by the ubiquitin-proteasome degradation pathway with the ubiquitin E1 UBA1 (ubiquitin-like modifier activating enzyme 1) and E3 ITCH. SUMOylation of SMN increased its acetylation to inhibit the formation of Cajal bodies (CBs). These results showed that SENP2 deficiency induced hyper-SUMOylation of the SMN protein, which further affected the stability and functions of the SMN protein, eventually leading to the SMA-like phenotype. Thus, we uncovered the important roles for hyper-SUMOylation of SMN induced by SENP2 deficiency in motor neurons and provided a novel targeted therapeutic strategy for SMA. KEY MESSAGES: SENP2 deficiency enhanced the hyper-SUMOylation of SMN and promoted the degradation of SMN by the ubiquitin-proteasome pathway. SUMOylation increased the acetylation of SMN to inhibit CB formation. SENP2 deficiency caused hyper-SUMOylation of SMN protein, which further affected the stability and functions of SMN protein and eventually led to the occurrence of SMA-like pathology.

ISOFLURANE ANESTHESIA IN BUDWING PRAYING MANTISES (PARASPHENDALE AGRIONINA).

Praying mantises have gained increasing popularity as pets and may be anesthetized to allow morphological identification and clinical procedures. The aim of this study was to evaluate the effects and anesthetic-related complications of isoflurane in oxygen in 15 client-owned budwing mantises (Parasphendale agrionina) undergoing photographic identification. Each mantis was placed in a self-constructed anesthetic chamber and exposed to a mixture of approximately 5% isoflurane in oxygen until anesthetic induction was achieved. Time to anesthetic induction, time to recovery from anesthesia, and quality of anesthesia based on scoring of righting reflex, front legs withdrawal, and muscular tone, were evaluated and recorded, as well as the occurrence of undesired effects. In most mantises, immobility, loss of righting reflex, and myorelaxation were achieved within minutes after the beginning of isoflurane exposure and lasted a time sufficient to allow completion of the procedure. However, mantises aged ≥12 mo had longer time to anesthetic induction (4.3 ± 0.6 m), as well as shorter time to recovery (19.0 ± 8.0 m), than mantises aged <12 mo (0.8 ± 0.4 and 30.0 ± 15.0; P < 0.05). Complications were not observed, and all mantises were returned to their owner on the same evening.

Flat on its back: the impact of substrate on righting methods of the brown marmorated stink bug, Halyomorpha halys.

Many animals, including insects, need to solve the problem of self-righting if inverted and substrate is one understudied factor that could affect righting ability. In this study we ask the questions, how does Halyomorpha halys self-right and does variation in substrate affect self-righting? To address our questions we used four substrates with different features and filmed H. halys righting response on each substrate (n = 22 individuals). We also used two synced cameras to film the most common righting method and quantified its kinematics. Self-righting metrics did vary depending on substrate in terms of diversity of righting methods used, duration of the successful righting event, number of fails per attempt, and stance width. We also determined that the symmetrical forward flip is the most common method used by H. halys. In the forward flip H. halys creates a tripod of support using the hindlegs and the tip of the abdomen to elevate the anterior portion of the body off the substrate and pitch forward onto its feet. In addition to demonstrating that substrate can impact self-righting and quantifying the symmetrical forward flip, we also provide a foundation for future explorations of sensory feedback and adaptive motor control using H. halys.

A Novel Etomidate Analog EL-0052 Retains Potent Hypnotic Effect and Stable Hemodynamics without Suppressing Adrenocortical Function.

Etomidate is a potent and rapidly acting anesthetic with high therapeutic index (TI) and superior hemodynamic stability. However, side effect of suppressing adrenocortical function limits its clinical use. To overcome this side effect, we designed a novel etomidate analog, EL-0052, aiming to retain beneficial properties of etomidate and avoid its disadvantage of suppressing adrenocortical steroid synthesis. Results exhibited that EL-0052 enhanced GABAA receptors currents with a concentration for EC50 of 0.98 ± 0.02 µM, which was about three times more potent than etomidate (3.07 ± 1.67 µM). Similar to hypnotic potency of etomidate, EL-0052 exhibited loss of righting reflex with ED50s of 1.02 (0.93-1.20) mg/kg in rats and 0.5 (0.45-0.56) mg/kg in dogs. The TI of EL-0052 in rats was 28, which was higher than 22 of etomidate. There was no significant difference in hypnotic onset time, recovery time, and walking time between EL-0052 and etomidate in rats. Both of them had minor effects on mean arterial pressure in dogs. EL-0052 had no significant effect on adrenocortical function in dogs even at a high dose (4.3 × ED50), whereas etomidate significantly inhibited corticosteroid secretion. The inhibition of cortisol synthesis assay showed that EL-0052 had a weak inhibition on cortisol biosynthesis in human H259 cells with an IC50 of 1050 ± 100 nM, which was 2.09 ± 0.27 nM for etomidate. EL-0052 retains the favorable properties of etomidate, including potent hypnotic effect, rapid onset and recovery, stable hemodynamics, and high therapeutic index without suppression of adrenocortical function. SIGNIFICANCE STATEMENT: The novel etomidate analog EL-0052 retains the favorable properties of etomidate without suppressing adrenocortical function and provides a new strategy to optimize the structure of etomidate.

Male HELLP pups experience sensorimotor delays and reduced body weight.

Offspring of Preeclampsia (PreE) and HELLP Syndrome are at an increased risk of developing neurodevelopmental disorders. In the current study we sought to determine if offspring from experimental models of PreE and HELLP had evidence of early onset neurodevelopmental delay. Offspring from PreE, HELLP and normal pregnant dams were assessed in a battery of sensorimotor tests beginning on postnatal day (PND) 3. Male HELLP offspring showed altered behavior in the surface righting reflex on PND 3 and cliff avoidance task from PND 3-6 relative to other groups. Results suggest that there are sex differences in offspring born to dams with PreE and HELLP.

MicroRNA-Dependent Control of Sensory Neuron Function Regulates Posture Behavior in Drosophila.

All what we see, touch, hear, taste, or smell must first be detected by the sensory elements of our nervous system. Sensory neurons, therefore, represent a critical component in all neural circuits and their correct function is essential for the generation of behavior and adaptation to the environment. Here, we report that the evolutionarily-conserved microRNA (miRNA) miR-263b plays a key behavioral role in Drosophila melanogaster through effects on the function of larval sensory neurons. Several independent experiments (in 50:50 male:female populations) support this finding: first, miRNA expression analysis, via reporter expression and fluorescent-activated cell sorting (FACS)-quantitative PCR (qPCR) analysis, demonstrate miR-263b expression in larval sensory neurons. Second, behavioral tests in miR-263b null mutants show defects in self-righting, an innate and evolutionarily conserved posture-control behavior that allows larvae to rectify their position if turned upside-down. Third, competitive inhibition of miR-263b in sensory neurons using a miR-263b "sponge" leads to self-righting defects. Fourth, systematic analysis of sensory neurons in miR-263b mutants shows no detectable morphologic defects in their stereotypic pattern, while genetically-encoded calcium sensors expressed in the sensory domain reveal a reduction in neural activity in miR-263b mutants. Fifth, miR-263b null mutants show reduced "touch-response" behavior and a compromised response to sound, both characteristic of larval sensory deficits. Furthermore, bioinformatic miRNA target analysis, gene expression assays, and behavioral phenocopy experiments suggest that miR-263b might exert its effects, at least in part, through repression of the basic helix-loop-helix (bHLH) transcription factor Atonal Altogether, our study suggests a model in which miRNA-dependent control of transcription factor expression affects sensory function and behavior.SIGNIFICANCE STATEMENT Sensory neurons are key to neural circuit function, but how these neurons acquire their specific properties is not well understood. Here, we examine this problem, focusing on the roles played by microRNAs (miRNAs). Using Drosophila, we demonstrate that the evolutionarily-conserved miRNA miR-263b controls sensory neuron function allowing the animal to perform an adaptive, elaborate three-dimensional movement. Our work thus shows that microRNAs can control complex motor behaviors by modulating sensory neuron physiology, and suggests that similar miRNA-dependent mechanisms may operate in other species. The work contributes to advance the understanding of the molecular basis of behavior and the biological roles of microRNAs within the nervous system.

Gabra6100Q allele Sprague-Dawley rats have a higher sensitivity to hypnosis induced by isoflurane and ethanol than the wild type rats.

BACKGROUND: The neurobiological mechanisms underlying how general anesthetics render a patient's unconsciousness (hypnosis) remains elusive. The role of the cerebellum in hypnosis induced by general anesthetics is unknown. Gabra6100Q allele Sprague-Dawley (SD) rats have a naturally occurring single nucleotide polymorphism in the GABAA receptor α6 subunit gene that is expressed exclusively in cerebellum granule cells. METHODS: We examined the loss of righting reflex (LORR) induced by isoflurane, and ethanol in Gabra6100Q rats compared with those in wild type (WT) SD rats. We also examined the change of c-Fos expression induced by isoflurane exposure in cerebellum granule cells of both mutant and WT rats. RESULTS: Gabra6100Q rats are more sensitive than WT rats to the LORR induced by isoflurane and ethanol. Moreover, isoflurane exposure induced a greater reduction in c-Fos expression in cerebellum granule cells of Gabra6100Q rats than WT rats. CONCLUSIONS: Based on these data, we speculate that cerebellum may be involved in the hypnosis induced by some general anesthetics and thus may represent a novel target of general anesthetics.