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Migratory journeys represent an energetic challenge for many long-distance migrants. The choice of flight times, migration route, altitude, travelling speed, wingbeat patterns, soaring as well as formation flight can all affect the energy expenditure for the journey. We monitored the flight patterns of two Northern Bald Ibises (Geronticus eremita) equipped with data loggers while crossing the Alps during a human-led migration from southern Germany to Tuscany. We observed that the birds used an intermittent flapping pattern, where phases of active flapping flight were regularly interrupted by short gliding phases. As a result of intermittent flight, the effective wing beat frequency was 13–20% lower than the observed wing beat frequency of 4.0 s−1. When local conditions allowed, the birds gained altitude through circling in thermal updrafts. During those circling bouts, gliding on the outstretched wing was predominant, though active wing flapping was still observed. Overall, the two birds spent 19 and 22% of the time soaring on the outstretched wing, accruing during that time 26 and 28% of the altitude gain required for the crossing of a major mountain range. This shows that, apart from formation flight, northern bald ibis use at least two more strategies—thermal soaring and intermittent flap-gliding—for improving energy economy during migratory flights. [ABSTRACT FROM AUTHOR]

Simple Summary: Reports of behavioral signs, such as blindness and circling in free-ranging moose from different parts of the world, have spurred comprehensive pathological investigation to find the causes of the disease that have clinical relevance. In this case study, brains collected from two adult free-ranging moose (Alces alces) cows that were seemingly blind and found walking in circles were examined by light and electron microscopy with further ancillary testing. Here, we report for the first time Lafora disease and alpha-synucleinopathy in two wild free-ranging moose cows who presented with abnormal behavior and blindness, with similar neuronal polyglucosan body (PGB) accumulations identified in humans and other animals. Microscopic analysis of the hippocampus of brain revealed inclusion bodies resembling PGBs (Lafora disease) in the neurons with ultrastructural findings of aggregates of branching filaments, consistent with polyglucosan bodies. Furthermore, α-synuclein immunopositivity was noted in the hippocampus, with accumulations of small granules ultrastructurally distinct from PGBs and morphologically compatible with alpha-synucleinopathy (Lewy body). The apparent blindness found in these moose could be related to an injury associated with secondary bacterial invasion; however, an accumulation of neurotoxicants (PGBs and α-synucleins) in retinal ganglion cells could also be the cause. Lafora disease and alpha-synucleinopathy were considered in the differential diagnosis of the young adult moose who presented with signs of blindness and behavioral signs such as circling. Lafora disease is an autosomal recessive glycogen-storage disorder resulting from an accumulation of toxic polyglucosan bodies (PGBs) in the central nervous system, which causes behavioral and neurologic symptoms in humans and other animals. In this case study, brains collected from two young adult free-ranging moose (Alces alces) cows that were seemingly blind and found walking in circles were examined by light and electron microscopy. Microscopic analysis of the hippocampus of the brain revealed inclusion bodies resembling PGBs in the neuronal perikaryon, neuronal processes, and neuropil. These round inclusions measuring up to 30 microns in diameter were predominantly confined to the hippocampus region of the brain in both animals. The inclusions tested α-synuclein-negative by immunohistochemistry, α-synuclein-positive with PAS, GMS, and Bielschowsky's staining; and diastase-resistant with central basophilic cores and faintly radiating peripheral lines. Ultrastructural examination of the affected areas of the hippocampus showed non-membrane-bound aggregates of asymmetrically branching filaments that bifurcated regularly, consistent with PGBs in both animals. Additionally, α-synuclein immunopositivity was noted in the different regions of the hippocampus with accumulations of small granules ultrastructurally distinct from PGBs and morphologically compatible with alpha-synucleinopathy (Lewy body). The apparent blindness found in these moose could be related to an injury associated with secondary bacterial invasion; however, an accumulation of neurotoxicants (PGBs and α-synuclein) in retinal ganglions cells could also be the cause. This is the first report demonstrating Lafora disease with concurrent alpha-synucleinopathy (Lewy body neuropathy) in a non-domesticated animal. [ABSTRACT FROM AUTHOR]

Lafora disease is an autosomal recessive glycogen-storage disorder resulting from an accumulation of toxic polyglucosan bodies (PGBs) in the central nervous system, which causes behavioral and neurologic symptoms in humans and other animals. In this case study, brains collected from two young adult free-ranging moose (Alces alces) cows that were seemingly blind and found walking in circles were examined by light and electron microscopy. Microscopic analysis of the hippocampus of the brain revealed inclusion bodies resembling PGBs in the neuronal perikaryon, neuronal processes, and neuropil. These round inclusions measuring up to 30 microns in diameter were predominantly confined to the hippocampus region of the brain in both animals. The inclusions tested α-synuclein-negative by immunohistochemistry, α-synuclein-positive with PAS, GMS, and Bielschowsky’s staining; and diastase-resistant with central basophilic cores and faintly radiating peripheral lines. Ultrastructural examination of the affected areas of the hippocampus showed non-membrane-bound aggregates of asymmetrically branching filaments that bifurcated regularly, consistent with PGBs in both animals. Additionally, α-synuclein immunopositivity was noted in the different regions of the hippocampus with accumulations of small granules ultrastructurally distinct from PGBs and morphologically compatible with alpha-synucleinopathy (Lewy body). The apparent blindness found in these moose could be related to an injury associated with secondary bacterial invasion; however, an accumulation of neurotoxicants (PGBs and α-synuclein) in retinal ganglions cells could also be the cause. This is the first report demonstrating Lafora disease with concurrent alpha-synucleinopathy (Lewy body neuropathy) in a non-domesticated animal.

In Australia, there are at least 50 000 derelict mines, many of which provide habitat for cave-roosting bats. Grating of derelict mines, be it horizontal (adits) or vertical (shafts) drives, is commonly undertaken to prevent human access, though longer-term responses of bats are largely unknown. We assessed the long-term (2–20 years) effects of grating on bats by documenting trends in emergence activity and bat abundance at grated and ungrated derelict mines and quantified behavioural responses of bats in autumn and winter. Emergence activity was dominated by the eastern horseshoe bat (Rhinolophus megaphyllus) with limited activity of other less manoeuvrable species. Both emergence activity and minimum colony size at horizontal adits were 8–9 times greater than at vertical shafts, with bats observed emerging from only 2 of 13 shafts. Emergence activity and minimum colony size were 7–10 times greater at adits with 'bat friendly' grating (horizontal bars with spacing >125 mm) than at other treatments (ungrated adits and adits with standard grating). In winter, there were 4–11 times more aborted exit attempts per bat at adits with 'bat friendly' grating compared with other treatments, which corresponded to greater emergence activity. Emergence activity and minimum colony size were not related to spacing between bars or time since grating, indicating rapid habituation by R. megaphyllus. However, circling at grates continued for many years and bentwing bats (Miniopterus spp.) made little use of these sites. Bat-friendly grates appear to be an effective management option for R. megaphyllus , but alternatives need to be trialled for other species. Derelict mines can provide habitat for cave-roosting bats but are often grated to prevent human access, with little known about the long-term responses of bats. We assessed the long-term effects of grating on bats and found that although there was rapid habituation to grated mines, altered flight behaviour was present decades after grating and there was little use of these sites by threatened species. This suggests that alternative management of derelict mines is required to conserve threatened bat roosting habitat. Photo by Leroy Gonsalves. [ABSTRACT FROM AUTHOR]

This article traces the origin and development of the by now ubiquitous Ashkenazic custom for the bride to circle the groom under the chuppa. The custom began as circling three times, and various reasons were given for this particular practice. Due to kabbalistic influence, the custom shifted from three circuits to seven, the common custom today. The reasons given also changed over time, reflecting changing attitudes to the symbolism of the wedding ceremony. [ABSTRACT FROM AUTHOR]

In experimental stroke studies, a neuroanatomy-based functional examination of behaviors is critical to predict the pathological extent of infarcts because brain-imaging studies are not always available. However, there is a lack of systematic studies to examine the efficiency of a behavioral test for this purpose. Our work aimed to design a new score for this goal in stroke rats, by simplifying the Garcia score (with subscore 1–6) and adding circling as subscore 7. MRI and 2,3,5-triphenyltetrazolium chloride staining were used to determine the pathological extent after transient middle cerebral artery occlusion. The modified summations of subscores were designed according to the predictability of each subscore for locations and sizes of infarcts in one group of stroke rats, and were validated in another group. The original Garcia score was able to predict the pathological extent of edema-adjusted infarct size ≥30%, and the summation of subscore 4, 6, and 7 (4: climbing, 6: vibrissae sensation, 7: circling) also could predict it well. The original Garcia score failed to predict infarct at the primary motor cortex, while the summation of subscore 4, 6, and 7 potentially could predict not only the primary motor cortex, but also the forelimb, hindlimb, and barrel field regions of the primary sensory cortex. Accordingly, this neuroanatomy-correlated functional assessment system composed of subscore 4, 6, and 7 was proposed, with less examination time and better inter-rater reliability than the original Garcia score. In summary, this new scoring system, summation (4,6,7) score, examined motor and sensory functions based on neuroanatomical involvement, having the potential to predict the pathological extent and specific relevant brain areas of infarcts, respectively.

Mining noise has a wide variety of frequency spectra and is a potential source of stress for wildlife. We evaluated the effects of mining machinery noise on behaviour and associated physiological parameters at two isoenergetic frequency ranges: high (>2 kHz) and low (≤2 kHz), the latter being less audible to mice, our model species. Effects of these two frequency spectra on behaviour, organ morphology and faecal corticosterone of wild mice were compared with a control treatment with no extra auditory stimuli. The mice exposed to high frequency noise spent less time in their nest than those exposed to low frequency noise or those in the control treatment, and they spent more time circling, especially anticlockwise, which in conjunction with elevated faecal corticosterone levels may reflect a greater right brain hemisphere stress-related response, particularly in females. Low frequency mining noise reduced grooming and circling, suggesting decreased physiological arousal due to mild stress. Low frequencies were also associated with increased faecal corticosterone in males compared to controls, which may be related to gender-based differences of the ear canal that affect frequency sensitivity. In conclusion, high frequency and low frequency mining machinery noise produced stress-related responses that may be important for the animals’ welfare and survival. [ABSTRACT FROM AUTHOR]

Tool actions are characterized by a transformation between movements and their resulting consequences in the environment. This transformation has to be taken into account when tool actions are planned and executed. We investigated how angular shift transformations between circling movements and their visual feedback affect the coordination of this feedback with visual events in the environment. We used a task that required participants to coordinate the visual feedback of a circular hand movement (presented on the right side of a screen) with a circling stimulus (presented on the left side of a screen). Four stimulus-visual feedback relations were instructed: same or different rotations of stimulus and visual feedback, either in same or different y-directions. Visual speed was varied in 3 levels (0.8 Hz, 1 Hz, and 1.2 Hz). The movement-visual feedback relation was manipulated using 8 angular shifts: (-180°, -135°, -90°, -45°, 0°, 45°, 90°, and 135°). Participants were not able to perform the different rotation/different y-direction pattern, but instead fell into the different rotation/same y-direction pattern. The different rotation/same y-direction pattern and the same rotation/same y-direction pattern were performed equally well, performance was worse in the same rotation/different y-direction pattern. Best performance was observed with angular shifts 0° and -45° and performance declined with larger angular shifts. Further, performance was better with negative angular shifts than with positive angular shifts. Participants did not fully take the angular shift transformation into account: when the angular shifts were negative the visual feedback was more in advance, and when angular shifts were positive the visual feedback was less in advance of the stimulus than in 0° angular shift. In conclusion, the presence and the magnitude of angular shift transformations affect performance. Internal models do not fully take the shift transformation into account.

Roots descend and circle once they meet nursery container walls, sometimes resulting in severe defects. This has been attributed to extended retention time in small containers. Four retention times in 11 and 57 L containers were tested for their impact on root architecture inside finished 170 L containers. All taxa (Acer rubrum, Magnolia grandiflora, Ulmus parvifolia) retained for four months in 11 L containers required delicate handling to shift into 57 L containers because roots had not bound substrate together, making the shortest retention time (four months) impractical. Although shifting was easier for longer retention times (seven, nine, and twelve months), root system quality measured by root deflections declined with increasing retention time in 11 and 57 L containers. A greater percentage of the five largest roots grew down container walls than either circled or grew straight into substrate of 170 L containers. Nearly all the largest roots were deflected by the 11 or 57 L container with almost none reaching the 170 L container wall. Shorter retention time in 11 and 57 L containers was associated with a smaller percentage of trunks circled, more roots reaching the 170 L periphery, and for elm and magnolia, more trunk growth. [ABSTRACT FROM AUTHOR]

Rationale: Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (K) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal. Objective: Present study has been structured to investigate the role of insulin and pharmacological modulator of K channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro. Methods: In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca) were assessed. Results: Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation. Conclusions: Insulin and gliclazide (K channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and K channel modulation may provide new avenues for research in morphine withdrawal. [ABSTRACT FROM AUTHOR]

One of the prominent pharmacological features of drugs acting at the brain cannabinoid receptor (CB1) is the induction of alterations in motor behavior. Catalepsy, immobility, ataxia, or the impairment of complex behavioral acts are observed after acute administration of either natural and synthetic cannabinoid receptor agonists or the endogenous CB1ligand anandamide. The dense presence of CB1receptors in the cerebellum and in the basal ganglia, especially at the outflow nuclei (substantia nigra and the internal segment of the globus pallidus), supports the existence of an endogenous cannabinoid system regulating motor activity. In the basal ganglia, the functionality of the anandamide–CB1system is poorly understood. Dual effects are often observed after the administration of CB1ligands in animal models of pharmacological manipulation of basal ganglia transmitter systems, indicating that the activity of the anandamide–CB1system depends on the ongoing activation of the different elements of the basal ganglia. This finding is in agreement with the proposed activity-dependent release of anandamide from a plasmalemma precursor. Additionally, a potential state-dependent bidirectional coupling of the CB1receptor to the adenylate cyclase transduction system has also been described. From this perspective, the endogenous cannabinoid system can be proposed as a local regulator of neurotransmission processes within the basal ganglia. This system may serve as a counterregulatory homeostatic mechanism preserving the functional role of basal ganglia circuits in coding the serial order of events that constitute movement.

Activity-dependent brain-derived neurotrophic factor (BDNF) signaling through receptor tyrosine kinase B (TrkB) is required for cued fear memory consolidation and extinction. Although BDNF is primarily secreted from glutamatergic neurons, TrkB is expressed by other genetically defined cells whose contributions to the behavioral effects of BDNF remain poorly understood. Parvalbumin (PV)-positive interneurons, which are highly enriched in TrkB, are emerging as key regulators of fear memory expression. We therefore hypothesized that activity-dependent BDNF signaling in PV-interneurons may modulate emotional learning. To test this hypothesis, we utilized the LoxP/Cre system for conditional deletion of TrkB in PV-positive cells to examine the impact of cell-autonomous BDNF signaling on Pavlovian fear conditioning and extinction. However, behavioral abnormalities indicative of vestibular dysfunction precluded the use of homozygous conditional knockouts in tests of higher cognitive functioning. While vestibular dysfunction was apparent in both sexes, female conditional knockouts exhibited an exacerbated phenotype, including extreme motor hyperactivity and circling behavior, compared to their male littermates. Heterozygous conditional knockouts were spared of vestibular dysfunction. While fear memory consolidation was unaffected in heterozygotes of both sexes, males exhibited impaired extinction consolidation compared to their littermate controls. Our findings complement evidence from human and rodent studies suggesting that BDNF signaling promotes consolidation of extinction and point to PV-positive neurons as a discrete population that mediates these effects in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Tool actions are characterized by a transformation between movements and their resulting consequences in the environment. This transformation has to be taken into account when tool actions are planned and executed. We investigated how angular shift transformations between circling movements and their visual feedback affect the coordination of this feedback with visual events in the environment. We used a task that required participants to coordinate the visual feedback of a circular hand movement (presented on the right side of a screen) with a circling stimulus (presented on the left side of a screen). Four stimulus-visual feedback relations were instructed: same or different rotations of stimulus and visual feedback, either in same or different y- directions. Visual speed was varied in 3 levels (0.8 Hz, 1 Hz, and 1.2 Hz). The movement-visual feedback relation was manipulated using 8 angular shifts: (-180°, - 135°, -90°, -45°, 0°, 45°, 90°, and 135°). Participants were not able to perform the different rotation/different y-direction pattern, but instead fell into the different rotation/same y-direction pattern. The different rotation/same y-direction pattern and the same rotation/same y-direction pattern were performed equally well, performance was worse in the same rotation/different y-direction pattern. Best performance was observed with angular shifts 0° and -45° and performance declined with larger angular shifts. Further, performance was better with negative angular shifts than with positive angular shifts. Participants did not fully take the angular shift transformation into account: when the angular shifts were negative the visual feedback was more in advance, and when angular shifts were positive the visual feedback was less in advance of the stimulus than in 0° angular shift. In conclusion, the presence and the magnitude of angular shift transformations affect performance. Internal models do not fully take the shift transformation into account. [ABSTRACT FROM AUTHOR]

Abstract: Some human subjects report vestibular disturbances such as vertigo, apparent motion, and nausea around or within high strength MRI systems operating at 4T to 9.4T. These vestibular effects have been ascribed to the consequences of movement through the high magnetic field. We have previously found that exposure to magnetic fields above 7T suppresses rearing, causes locomotor circling, and induces conditioned taste aversion (CTA) in rodents. The present experiments were designed to test the effects on rats of motion through the magnetic field of the 14.1T superconducting magnet. In Experiment 1, we compared the effects of multiple rapid insertions and removals from the center of the magnet to the effects of continuous exposure. Repeated traversal of the magnetic field gradient with only momentary exposure to 14.1T was sufficient to suppress rearing and induce a significant CTA. Repeated insertion and removal from the magnet, however, did not have a greater effect than a single 30-min exposure on either acute locomotor behavior or CTA acquisition. Prolonged exposure was required to induce locomotor circling. In the second series of experiments, we controlled the rate of insertion and removal by means of an electric motor. Locomotor circling appeared to be dependent on the speed of insertion and removal, but the suppression of rearing and the acquisition of CTA were independent of speed of insertion and removal. In Experiment 3, we inserted rats into the center of the magnet and then rotated them about their rostral–caudal axis during a 30-min 14.1T exposure. Rotation within the magnet did not modulate the behavioral effects of exposure. We conclude that, in rats, movement through the steep gradient of a high magnetic field has some behavioral effects, but sustained exposure to the homogenous center of the field is required for the full behavioral consequences. [ABSTRACT FROM AUTHOR]

Abstract: In the mouse, development of the lateral semicircular canal of the inner ear is sensitive to Bmp4 heterozygosity. In the C57BL6 background 30% of the heterozygotes display circling behavior, 66% have a specific defect in the vestibular part of the inner ear, namely the constriction, interruption or absence of the lateral semicircular canal. Only mice having both ears affected display circling behavior. In the (C57BL6xCBA)N1 background, the penetrance of the canal phenotype is greatly reduced, and bilateral lateral canal defect is not sufficient to induce circling. We found association of the canal phenotype with the genotype of markers on chromosome 14 and 4, co-localizing with Ecs and Eclb identified in the Ecl mouse with similar lateral canal defects. Candidate genes to contain the causal mutation are Bmp4 on chromosome 14, and Rere on chromosome 4. [Copyright &y& Elsevier]

Abstract: In order to test the hypothesis that early postnatal ethanol exposure has long lasting behavioral effects that include changes to the normal pattern of cerebral asymmetries, the free swimming test (FST) was used to study the behavior of adult Swiss mice (males and females) exposed to ethanol during the third trimester equivalent of human gestation. Animals received ethanol (5 g/Kg ip, ETOH group) or saline (CONT group) on alternate days from postnatal day (P) 2 to P8, and were submitted to 1 session of open field (OF) and 3 sessions of FST from P75 to P81. No differences between ETOH and CONT groups were observed in OF. However, the FST revealed significant differences between ETOH and CONT mice during the first session. The percentage of animals that presented strong turning preferences (especially to the right side) was higher in the ETOH group when compared with the CONT group. These data give support to the hypothesis that early ethanol exposure affects cerebral asymmetries and suggests that the FST is a useful tool to investigate the long-lasting effects of ethanol exposure during development. [Copyright &y& Elsevier]

Abstract: There is increasing evidence that developmental anomalies of cerebral asymmetry are involved in the etiology of psychiatric disorders, including schizophrenia, depression and anxiety. Thus, rodents with abnormal cerebral lateralization are interesting tools to study the association between such anomalies and behavioral dysfunction. The most studied indicator of cerebral asymmetry in the rat is that of circling or rotational behavior. We have recently described two rat mutants, ci2 and ci3, in which lateralized rotational behavior occurs either spontaneously or in response to external stimuli, such as new environment or handling. While cochlear and vestibular defects are found in 52 rats, ci3 rats do not exhibit any inner ear abnormalities. The abnormal motor response to external stimuli raised the possibility that the circling rat mutants may be more likely to express anxiety-related behavior in tests of emotionality. In the present study, we characterized anxiety-related behaviors of ci2 and ci3 rats in the open field, elevated plus-maze and light/dark exploration test. Furthermore, sensorimotor functions of these rats were evaluated by the rotarod, accelerod and wire hang tests. Heterozygous (ci2/+) littermates or rats of the respective background strains (LEW, BH.7A) were used as controls. In contrast to our expectation, both mutants demonstrated less anxiety-related behavior than controls in tests of emotionality. Ci3 rats exhibited normal sensorimotor functions, whereas marked impairment was observed in ci2 rats, which is most likely a consequence of the vestibular dysfunction in these animals. The acoustic startle response (ASR) and prepulse inhibition of ASR did not differ between ci3 rats and controls. The reduced emotionality of the mutant rats indicated by the present experiments may not be specifically linked to anxiety per se, but is maybe more reflective of impulsivity or the inability to normally perceive or process potentially threatening situations. Based on previous findings of dysfunctions of the central dopamine system in ci2 and ci3 mutant rats, we assume that alterations in dopaminergic activity are involved in the maladaptive behavior observed in the present study. [Copyright &y& Elsevier]

Abstract: Static high magnetic fields (MFs) from 7 T to 9 T can elicit behavioral responses in rodents such as suppression of rearing, locomotor circling, and acquisition of a conditioned taste aversion (CTA). MF exposure also induces c-Fos expression in the visceral and vestibular nuclei of the brainstem, suggesting the stimulation of some sensory pathways. It is not clear, however, if the effects of the MF are caused by exposure to the uniform maximal field at the center of the magnet, or by exposure to the steep field gradients along the bore of the magnet during the rat''s placement. In addition, the site of action within the rat is unknown. In an attempt to limit MF exposure to rostral or caudal portions of the rats'' body, we exposed male and female rats at different positions within the bore of a 14.1-T superconducting magnet ranging from 2 cm (1.6 T at the head) to 155 cm (0.05 T at the head), with the center of the bore at 65 cm (14.1 T across the whole body). This approach also allowed us to expose rats to the maximal field strength (14.1 T) vs. the maximal field gradients (54 T/m). To assess both immediate and delayed behavioral effects, locomotor and CTA responses were recorded. A small but significant CTA was seen after exposure of the head to the lowest MF tested (0.05 T at 155 cm). Graded effects were seen, however, with greater circling and CTA acquisition as the MF strength increased at the rostral end of the rat. This suggests a cephalic site of action. Furthermore, maximal circling and CTA were induced after exposure to the uniform center field, and not after exposure to high field gradients on either side of the center. This suggests that the behavioral responses seen after MF exposure are a consequence of the uniform static field at the center of the magnet, and are not caused by passage through, or exposure to, the vertical field gradients. Female rats responded similarly to male rats, although magnet-induced CTA appeared resistant to extinction in female rats. [Copyright &y& Elsevier]

Cocaine binges represent the most severe form of cocaine taking due to high levels of cocaine consumed and a potential loss of self-control over cocaine taking. Experimentally, regulation of intravenous cocaine self-administration is observed during binges as revealed by nearly constant sequential inter-infusion intervals, suggesting that pharmacological and unconditioned behavioral effects of cumulative cocaine leave intact its reinforcing effect. To elucidate factors that contribute to the patterning of cocaine self-administration behavior during binges, the current study quantifies the expression of specific motor routines that emerge from the beginning of a cocaine infusion until the next cocaine reinforcement is received, in six separate rats over 24 h of continuous access. During each 24-h cocaine binge, behavior was continuously monitored using a force plate actometer that provides reliable quantitation of rodent behaviors, including rotational behavior, locomotor activity, and focused stereotypy. Corroborating earlier results, each rat accumulated between 4 and 11 mg/kg/h during periods of active cocaine self-administration. All rats displayed a similar narrow range of unconditioned behavioral responses to cocaine, yet each rat varied with regard to the intensity and specific predominant pattern of behavioral activation. Focused stereotyped behavior, in particular, was apparent in all rats and continued for as long as cocaine self-administration behavior remained active. The current results support the hypothesis that individual differences in cocaine’s pharmacodynamics may contribute to specific behaviors expressed during cocaine self-administration, but leave unresolved whether or not intense unconditioned behavior (e.g., focused stereotypy) conflicts with, or contributes to, ongoing self-administration behavior. [ABSTRACT FROM AUTHOR]

Abstract: We have recently described two rat mutants, ci2 and ci3, in which abnormal lateralized rotational behavior and locomotor hyperactivity occur either spontaneously or in response to external stimuli, such as new environment. While cochlear and vestibular defects are found in ci2 rats, ci3 rats do not exhibit any inner ear abnormalities. Both mutants show abnormal lateralities in striatal dopamine and in the density of dopaminergic neurons in substantia nigra or ventral tegmental area, which may be involved in the behavioral phenotype of these rats. In line with this hypothesis, the circling behavior of the ci2 and ci3 mutants is intensified by amphetamine. In the present study, we evaluated the effects of dopamine receptor blockade on the abnormal behaviors of ci2 and ci3 rats. Haloperidol blocked the hyperactivity in both mutants, but this was most likely due to the known inhibitory effect on locomotion by this drug. When animals were observed during the light phase, the abnormal rotational behavior of the mutants was not significantly affected by haloperidol, whereas the dopamine D2 receptor-preferring antagonist raclopride significantly reduced rotations in ci2 rats. When the behavior of the ci3 rats was video-monitored during the dark phase, circling was significantly inhibited by haloperidol. The most striking difference between the two mutants was that ci2 rats were less susceptible than the unaffected littermates to the cataleptogenic effects of haloperidol and raclopride, whereas no such difference was observed in ci3 rats. These data demonstrate that, although there are several similarities between the ci2 and ci3 rat mutants, their cataleptogenic response to dopamine receptor blockade strikingly differs. The comparative evaluation of these two rat mutants may help to increase our understanding of the relationship between developmental anomalies of cerebral asymmetry and brain disorders. [Copyright &y& Elsevier]

Abstract: Classical agonists of the dopamine D1 receptor activate both adenylyl cyclase and phospholipase C (PLC) signaling pathways. As a result, the extent to which these two pathways are essentially involved in various effects produced by D1 receptor agonists is currently uncertain. In the present report we examined the effects of SKF 83822, a dopamine D1 agonist which has been reported to activate adenylyl cyclase, but not PLC, on behavior and immediate early gene (IEG) expression in rats with unilateral 6-hydroxydopamine lesions. SKF 83822 (25–100 μg/kg) induced dose dependent contralateral rotation in these subjects, and, additionally, stimulated strong expression of the IEG products c-Fos, Fra2, Zif/268 and Arc in the deinnervated striatum. All of these effects could be antagonized by pretreatment with the selective D1 dopamine antagonist SCH 23390 (0.5 mg/kg). Although PLC may be involved in many effects mediated through dopamine D1 receptors, these results suggest that direct activation of PLC is not necessary for the induction of either rotation or IEG expression in dopamine depleted rats. [Copyright &y& Elsevier]

Abstract: Repetitive behaviors (such as circling) are one of the defining features of autism. The substantia nigra (SN) is involved in circling. We used unilateral SN pars reticulata (SNR) infusions of the GABA agonist muscimol to induce circling and deoxyglucose autoradiography mapping in adult and postnatal day (PN) 15 male and female rats to determine its substrates. In adults, muscimol infusions in posterior SNR induced a higher circling rate than in anterior SNR, after which males displayed faster circling than females. In contrast, PN15 female rats circled faster than PN15 male rats. Autoradiograms demonstrated age- and sex-specific alterations of deoxyglucose uptake in the SN pars compacta (SNC) associated with highest circling rates. The data suggest that there is a close relationship of the GABAergic SNR and dopaminergic SNC in the induction of circling; there is a topographic organization of the SNR in terms of circling behavior and associated deoxyglucose uptake, which is dependent on age and sex. [Copyright &y& Elsevier]

The purpose of this study was to characterise two new mouse mutants, carousel, and whirligig. Both were derived from a large-scale mutagenesis programme which screened for dominantly inherited mutations that cause hearing impairments and balance defects. Genetic mapping placed both mutations on the proximal region of chromosome 4. Paint-filling and clearing techniques revealed abnormalities of the lateral semicircular canal. Scanning electron microscopy showed increased numbers of outer and inner hair cells in the apical region of the organ of Corti. The behavioural, genetic, and morphological characteristics lead us to the conclusion that both mutants are probably alleles of seven previously identified mutants which all map to proximal chromosome 4 and share similar defects of the lateral semicircular canal. We suggest that this region may be particularly susceptible to ENU mutagenesis and is independent of genetic background. [ABSTRACT FROM AUTHOR]

High-strength static magnetic fields are common tools in clinical imaging, but the behavioral effects are not well characterized. Previous studies on rats showed that fields of 7 T or above produced locomotor circling, conditioned taste aversion (CTA) and c-Fos in vestibular nuclei. To determine the generality of the behavioral effects on a smaller species, we subjected restrained or unrestrained mice to 30-min exposures in a 14.1-T field. Mice were given saccharin immediately prior to magnet or sham exposure on 3 consecutive days. All mice exposed to the magnet developed a CTA, and a significant number displayed tight circling and suppression of rearing. Unrestrained mice exhibited larger effects than restrained mice. These effects, similar to the effects in rats, may be the result of a vestibular disturbance caused by the magnetic field. [Copyright &y& Elsevier]

Abstract In an attempt to define clinically relevant models of akinesia and dyskinesia in 6-hydroxydopamine (6-OHDA)-lesioned rats, we have examined the effects of drugs with high (l-DOPA) vs. low (bromocriptine) dyskinesiogenic potential in Parkinson's disease on three types of motor performance, namely: (i) abnormal involuntary movements (AIMs) (ii) rotational behaviour, and (iii) spontaneous forelimb use (cylinder test). Rats with unilateral 6-OHDA lesions received single daily i.p. injections of l-DOPA or bromocriptine at therapeutic doses. During 3 weeks of treatment, l-DOPA but not bromocriptine induced increasingly severe AIMs affecting the limb, trunk and orofacial region. Rotational behaviour was induced to a much higher extent by bromocriptine than l-DOPA. In the cylinder test, the two drugs initially improved the performance of the parkinsonian limb to a similar extent. However, l-DOPA-treated animals showed declining levels of performance in this test because the drug-induced AIMs interfered with physiological limb use, and gradually replaced all normal motor activities. l-DOPA-induced axial, limb and orolingual AIM scores were significantly reduced by the acute administration of compounds that have antidyskinetic efficacy in parkinsonian patients and/or nonhuman primates (-91%, yohimbine 10 mg/kg; -19%, naloxone 4–8 mg/kg; -37%, 5-methoxy 5-N,N-dimethyl-tryptamine 2 mg/kg; -30%, clozapine 8 mg/kg; -50%, amantadine 40 mg/kg). l-DOPA-induced rotation was, however, not affected. The present results demonstrate that 6-OHDA-lesioned rats do exhibit motor deficits that share essential functional similarities with parkinsonian akinesia or dyskinesia. Such deficits can be quantified using novel and relatively simple testing procedures, whereas rotometry cannot discriminate between dyskinetic and antiakinetic effects of antiparkinsonian treatments. [ABSTRACT FROM AUTHOR]

The waltzing behavior is usually attributed to vestibular dysfunction. However, the vestibular control of gaze and posture has not yet been measured quantitatively in any waltzing mutant. Therefore, this study was aimed at investigating the relationship between inner-ear morphology, the circling behavior, and the vestibular control of gaze and posture in a new strain of waltzing rats. Light- and electron-microscopy studies of these mutants did not reveal any structural abnormalities of the vestibular neural epithelia. In addition, the expression of Calretinin and 200-kD phosphorylated and non-phosphorylated neurofilaments was also found to be normal in the vestibular neural epithelia and ganglion cells. In contrast, the mutants showed severe dysfunctions of the vestibular control of gaze and posture. The skeletal geometry of the alert unrestrained animals was studied using cineradiography. At rest, waltzing rats held their heads tilted down: the horizontal semicircular-canal's plane was near the earth-horizontal's plane, instead of being tilted up as in Long Evans control rats. In addition, their cervical column was pitched more forward (33.6°) than in the control group (6.9°). The circling behavior was observed frequently, and the rats had episodes of circling in both directions. The episodes of circling amounted to an average of 17 turns, and the average angular velocity of the circling was 645°/s. Unilateral labyrinthectomy induced the same postural and oculomotor syndromes in the waltzing and control groups. This indicates that the mutant vestibular nerve had a significant resting discharge before the lesion. Eye movements were recorded using acutely implanted search coils. Although waltzing rats were able to perform normal spontaneous eye movements, they showed a complete deficit of the horizontal vestibulo-ocular reflex (HVOR) and an impairment of the maculo-ocular reflex (MOR) during constant velocity, off-vertical axis rotation (OVAR). These results show, for the first time, that deficient transduction and/or processing of the horizontal-canal- and macular-related information can be causally related to the circling behavior and abnormal posture, respectively. [ABSTRACT FROM AUTHOR]

Reindeer (Rangifer tarandus) kept in corrals or otherwise forced to clump typically start milling in response to stressing events. This behaviour is generally considered to have an antipredator effect. An inquiry on herd behaviour, to which 35 Norwegian reindeer husbandry districts responded, showed that 32 experienced that corralled rein¬deer consistently circled leftwards, whereas the remaining three reported consistently rightward circling. Regular monitoring of a reindeer herd in central Norway over a two-year period (1993-94), and experimental studies on a fraction of the same herd, revealed the following traits. Free-ranging reindeer showed no right- or left-turning preference during grazing or browsing, but when the reindeer were driven into corrals or forced to clump in the open they invariably rotated leftwards. The circling of corralled reindeer was triggered at an average group size of 20 to 25 animals, apparently independently of the age and sex of the animals. When they dug craters in the snow to reach food, the reindeer used their left foreleg significantly more often than their right. In 23 out of 35 reindeer, the right hemisphere of the brain was heavier than the left. However, in the sample as a whole, the weights of the left and right hemispheres did not differ significantly. Lateralised behaviour in reindeer is thought to be determined by natural and stress induced asymmetries in brain structure and hormonal activity. In addition, learning is probably important for passing on the behaviour between herd members and generations. Differences in lateralised behaviour between nearby herds are thought to be related primarily to different exposure to stress and learning, whereas genetical and environmental fac¬tors (e.g. diet), age structure and sex ratio are probably more important for explaining differences between distant pop¬ulations.

Circling and asymmetric behaviours to apomorphine (dopamine agonist/antagonist) challenge were studied in rats with unilateral striatal electrolesions or 6-hydroxydopamine (6-OHDA) lesions, each induced by combined lesions at 3 striatal locations, to allow an assessment of drug action on 'normal' receptors in the intact striatum or 'supersensitive' receptors in the lesioned striatum respectively. The minimally effective dose of 6-OHDA (given in the presence of DMI and tranylcypromine) to cause functional change was 3×8 μg, with 3×32 μg providing maximal change. Electrolesions were shown histologically to be confined to striatal tissue, and dopamine depletions caused by 6-OHDA were selective for the striatum. Temporal differences were recorded for onset of asymmetry and circling behaviour, both between behaviours and between lesions. Thus, asymmetry developed during the 2nd-4th days after 6-OHDA lesion but circling developed more abruptly on postoperative days 10-12. In contrast, both asymmetry and circling behaviours were apparent from the first day following electrolesion. The dose-dependent effects of apomorphine were apparent at much lower doses in 6-OHDA lesioned than electrolesioned rats. This potency difference was also demonstrated for two further dopamine agonists, 2-di-n-propylamino-5,6-dihydroxytetralin and SK & F 38393. In contrast, the agonist-induced asymmetric and circling behaviours of electrolesioned rats were some 9-44 times more sensitive than those of 6-OHDA lesioned rats to antagonism by the neuroleptic agents haloperidol, α-flupenthixol and oxiperomide, although tiapride antagonism was very similar in both the electrolesioned and 6-OHDA-lesioned rats. Thus, selective striatal denervation techniques are used to show that asymmetric and circling behaviours can be differentially induced and manipulated, and that the increased sensitivity (over electrolesions) of 6-OHDA lesioned rats to dopamine agonist action to induce these behavioural effects is associated with a reduced sensitivity to neuroleptic activity to reduce the asymmetric and circling responses. [ABSTRACT FROM AUTHOR]

Sibutramine hydrochloride, a novel monoamine reuptake inhibitor antidepressant, has been studied to determine whether it alters dopaminergic function in the brain. Its effects have been compared with bupropion, a dopamine reuptake inhibitor, and methamphetamine, a dopamine reuptake inhibitor and releasing agent. Sibutramine (0.1-3 mg/kg PO) and methamphetamine (0.3-30 mg/kg PO) both prevented reserpine (0.75 mg/kg IV) ptosis in rats with ED values of 0.6 mg/kg and 4.2 mg/kg, respectively. Bupropion (10-100 mg/kg PO) was ineffective against reserpine ptosis. The efflux of [H]-dopamine from preloaded rat striatal slices was not altered by 10-10 M concentrations of sibutramine, BTS 54 354, BTS 54 505 (secondary and primary amine metabolites, respectively) or bupropion. In contrast, methamphetamine (10-10 M) caused a significant concentration-dependent increase in [H]-dopamine release. Sibutramine (3 mg/kg IP or 6 mg/kg PO) and bupropion (10 mg/kg IP or 430 mg/kg PO) did not alter 3-methoxy-tyramine (3-MT) levels in rat striatum. Striatal 3-MT concentrations were, however, dose-dependently increased by methamphetamine (0.3-10 mg/kg IP or 0.42-4.2 mg/kg PO). Sibutramine (6 mg/kg PO) did not induce circling in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic neuronal tract. Bupropion (10-100 mg/kg PO) did not induce circling at the lowest dose, but caused increasing ipsilateral rotation at higher doses. Methamphetamine (0.42 or 4.2 mg/kg PO) induced ipsilateral circling with marked effects at the higher dose. In a two-choice lever pressing model using rats trained to discriminate d-amphetamine (0.5 mg/kg IP) from saline, sibutramine (0.3-3 mg/kg IP) generalised to the saline lever. Bupropion (3-30 mg/kg IP) generalised to d-amphetamine at the highest dose, while methamphetamine (0.1-5 mg/kg IP) generalised to this lever at doses as low as 0.3 mg/kg. Overall, the rank order of potency for enhancing central dopaminergic function is methamphetamine > bupropion >> sibutramine. The data therefore indicate that dopamine is unlikely to be an important pharmacological target for reuptake inhibition by sibutramine. [ABSTRACT FROM AUTHOR]

Microinjections of d-amphetamine (5.0, 10.0 and 20.0 µg/0.5 µl) into the nucleus accumbens caused reliable dose-dependent circling away from the side of injection. Injections of l-amphetamine were not effective, ruling out non-specific effects of pH, osmolarity and the like and also ruling out noradrenergic actions as explanations of the behavioral effects. Injections of d-amphetamine into the ventral caudate were less potent than those into the nucleus accumbens, suggesting nucleus accumbens rather than more dorsal tissue as the site of this behavioral effect. These data suggest that asymmetrical activation of the nucleus accumbens is a sufficient condition to induce circling behavior and raise questions for the commonly accepted view that asymmetrical activation of the caudate is a necessary condition for dopamine dependent circling behavior. [ABSTRACT FROM AUTHOR]

Apomorphine, 2 mg/kg (s.c.) produced significant contralateral turning in rats with unilateral radiofrequency lesions of the habenula nucleus over a test period of 60 min when tested at post-surgery days 3, 7, and 14. Levels of contralateral circling were not significantly increased when the animals were tested on days 21 and 28, although a contralateral bias was still observed. Rotation induced by apomorphine was completely blocked by the administration of haloperidol (0.3 mg/kg i.p.), and there was no behavioural asymmetry in lesioned animals following administration of saline or a high dose of haloperidol (2 mg/kg i.p.). These results indicate that unilateral habenula lesions lead to imbalance of dopaminergic activity, which is expressed as contralateral circling when the animal is challenged with apomorphine. [ABSTRACT FROM AUTHOR]

The role of the midbrain angular complex (AC) in the execution of motor behaviours was investigated in the rat. In an automated holeboard apparatus bilateral AC electrolesions attenuated exploration and increased locomotor performance of drug-free rats on the first and second test occasions respectively; the latter result may signify a retarding of between-session habituation. Apomorphine also decreased locomotion and almost abolished head dipping and rearing in the holeboard; bilateral AC lesions reinstated locomotion to a normal level without modifying the other behavioural parameters. An electrolesion of one AC did not affect the animal's posture or spontaneous locomotion in the open field, but gave rise to pronounced ipsiversive circling when coupled with systemic administration of apomorphine. In unilaterally 6-hydroxydopamine (6-OHDA) treated rats subcutaneous injection of apomorphine evoked robust contraversive circling. A concomitant lesion of the ipsilateral AC introduced an additional ipsilateral bias to these animals' movements; contraversive circling was initially curtailed and posture reduced (or reversed), while stereotyped activities (particularly grooming) were suppressed. Contralateral orientation and circling were restored by subsequently lesioning the contralateral AC as well; bilateral AC lesions significantly potentiated circling to systemic apomorphine. Contralateral locomotor asymmetry was also produced by depositing apomorphine stereotaxically into the supersensitive caudate, or by microinjecting one substantia nigra zona reticulata with muscimol (in naive rats). Both rotational responses were facilitated by injury to the ipsilateral AC. The effects of electrocoagulating the AC were generally duplicated by discrete microinjection of muscimol or γ-vinyl GABA into this area, suggesting GABA-mediated synapses are normally operative in this part of the brain. These results do not support the claim that the AC is specifically engaged in mediating postural asymmetry in the unilaterally 6-OHDA denervated rat. Instead, we believe that impairment of neurotransmission through one AC imposes an independent and reciprocal tendency to move towards that side of the brain, as well as attenuating stereotypy and facilitating locomotion. The resultant behavioural response to systemic apomorphine shown by animals bearing these two types of lesion embodies these separate actions. [ABSTRACT FROM AUTHOR]

Unilateral intranigral administration of baclofen (50-200 ng), muscimol (2.5-20 ng), or THIP (50-400 ng) in the rat led to contralateral circling behavior of a qualitatively similar nature. The potency of all three GABA-mimetics was enhanced in animals which had received the depot neuroleptic fluphenazine decanoate (10 mg/kg SC) 7 days prior to their intranigral administration. Significant differences between the nigral actions of the drugs could be demonstrated by their altered activity in the presence of a benzodiazepine. Flurazepam (500 ng) enhanced the intranigral potency of THIP, but reduced that of intranigral baclofen. Muscimol-induced circling behavior was unaffected by concomitant flurazepam. The data provide evidence for a functional supersensitivity of GABA-sensitive nondopaminergic projections from the substantia nigra in response to chronic neuroleptic treatment and reveal differences between the precise sites or modes of action of baclofen, muscimol, and THIP within this structure. [ABSTRACT FROM AUTHOR]

Sodium valproate is an anticonvulsant which elevates GABA levels in the brain. GABA interacts with dopamine functionally in certain areas of the brain involved in motor behavior such as the nucleus accumbens and the substantia nigra. In order to determine whether GABA can play a functional role in the pharmacological effects of valproate, both valproate and GABA were injected directly into these two brain areas and the effects of these compounds on motor function were studied. Both GABA and sodium valproate inhibited in a dose dependent manner the hyperactivity induced by the bilateral injection of dopamine into the nucleus accumbens. Picrotoxin, a GABA antagonist, blocked the inhibitory effect of valproate. When injected into the pars reticulata of the substantia nigra, both sodium valproate and GABA enhanced apomorphine-induced circling in rats with a unilateral lesion of lateral hypothalamus caused by 6-hydroxydopamine. This effect was blocked by the systemic administration of picrotoxin. These observations suggest that sodium valproate can produce effects that result from the activation of GABA receptor sites in the brain. [ABSTRACT FROM AUTHOR]

In an attempt to define the nature of the involvement of Δ-tetrahydrocannabinol (THC) with central cholinergic neurotransmission, the effects of THC on direct cholinergic stimulation of the rat brain were investigated. THC, in doses of 3 mg/kg and 6 mg/kg, administered intraperitoneally (i.p.), potentiated the effects of carbachol injection into the lateral septal nucleus, as manifested by enhancement of the drinking response elicited by the septal carbachol injection and by potentiation of the tendency of this carbachol injection to induce abnormal motor responses. Although atropine (10 mg/kg, i.p.) completely blocked the carbachol induced drinking, the atropine did not completely block the drinking response when THC was given with carbachol. The results indicate an apparent sensitization, by THC, of a limbic cholinergic system. [ABSTRACT FROM AUTHOR]

Extensive unilateral or bilateral electrolytic ablation of the rat superior colliculus failed to reduce apomorphine- or amphetamine-induced rotation in animals with a unilateral 6-hydroxydopamine lesion of one nigro-striatal dopaminergic pathway. These findings suggest that a nigro-tectal pathway does not play a crucial role in mediating the circling response caused by striatal dopamine receptor stimulation. However, electrolytic lesions of the dorsal tegmental decussation reduced apomorphine- but not amphetamine-induced rotation in such animals, perhaps by sectioning some commissural pathway between the two nigro-striatal systems. [ABSTRACT FROM AUTHOR]

Abstract: The Balb/c mouse is behaviorally hypersensitive to effects of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, and displays impaired sociability. In the current investigation, MK-801-elicited circling behavior in the genetically inbred Balb/c mouse strain that was either not or only minimally observed in similarly treated outbred Swiss-Webster mice. The ability of compounds to attenuate the intensity of MK-801-elicited circling behavior in the Balb/c mouse strain may serve as a preclinical screening paradigm for identifying effective NMDA receptor agonist interventions in the intact animal; ideally, these compounds would have therapeutic value in neuropsychiatric disorders associated with impaired sociability, such as schizophrenia and autism spectrum disorders (ASD). [Copyright &y& Elsevier]

• 'Flotation and circling indexes' discriminate 6-month-old 3xTg-AD mice from controls • 'Flotation index' is characteristic of non-transgenic performance at onset of disease. • 'Flotation index' is sensitive (reduction) to accelerated aging and AD genotype. • 'Circling behavior' is more characteristic of 3xTg-AD mice also at onset of disease. • 'Circling index' unveils bizarre behavior induced by d -galactose induced aging. The study of behavioral and psychological symptoms of dementia (BPSD) has been largely neglected in most experimental research on Alzheimer's disease (AD) classically focused on cognitive symptoms. The aquatic environment of the Morris water maze (MWM) implies a stressful condition for mice leading to cognitive performances with presence of other behaviors related to emotionality. This can be critical in models such as the 3xTg-AD mice that exhibit a noticeable BPSD-like profile. The present work is aimed to provide a quantitative (number of episodes and duration) and qualitative (prevalence) analysis of flotation and circling, the most common 'non-searching behaviors' elicited in the MWM. We studied the expression of these behaviors in 6-month-old gold-standard wildtype C57BL/6 mice (genetic background) and 3xTg-AD mice (onset of disease) and when both genotypes were submitted to chronic d -galactose induced accelerated aging. Elicitation of floating and circling was recorded during three standard MWM paradigms: visual perceptual learning, place task for spatial reference memory and a final probe trial for short-term memory. In view of the results, we demonstrate that the index of 'flotation', characteristic of non-transgenic performance, is sensitive (reduction) to accelerated aging and AD. Conversely, circling behavior, characteristic of 3xTg-AD mice, can be an additional tool for evaluating BPSD-like symptoms in AD-models while its index unveils bizarre behavior induced by d -galactose induced aging. These results can be useful in relation to preventive and/or therapeutical interventions targeting AD but they may also be suitable in the evaluation of the potential risk factors in animals with normal aging. [ABSTRACT FROM AUTHOR]

In experimental stroke studies, a neuroanatomy-based functional examination of behaviors is critical to predict the pathological extent of infarcts because brain-imaging studies are not always available. However, there is a lack of systematic studies to examine the efficiency of a behavioral test for this purpose. Our work aimed to design a new score for this goal in stroke rats, by simplifying the Garcia score (with subscore 1-6) and adding circling as subscore 7. MRI and 2,3,5-triphenyltetrazolium chloride staining were used to determine the pathological extent after transient middle cerebral artery occlusion. The modified summations of subscores were designed according to the predictability of each subscore for locations and sizes of infarcts in one group of stroke rats, and were validated in another group. The original Garcia score was able to predict the pathological extent of edema-adjusted infarct size ≥30%, and the summation of subscore 4, 6, and 7 (4: climbing, 6: vibrissae sensation, 7: circling) also could predict it well. The original Garcia score failed to predict infarct at the primary motor cortex, while the summation of subscore 4, 6, and 7 potentially could predict not only the primary motor cortex, but also the forelimb, hindlimb, and barrel field regions of the primary sensory cortex. Accordingly, this neuroanatomy-correlated functional assessment system composed of subscore 4, 6, and 7 was proposed, with less examination time and better inter-rater reliability than the original Garcia score. In summary, this new scoring system, summation (4,6,7) score, examined motor and sensory functions based on neuroanatomical involvement, having the potential to predict the pathological extent and specific relevant brain areas of infarcts, respectively.

With age, there is a progressive loss of body balance function. Yet, the potential influence of osteoporosis on body balance is largely unknown. Dentin matrix protein 1 (DMP1) is highly expressed in bone and required for phosphate homeostasis and mineralization. Dmp1 null mice display striking defects in bone structure. In this study we reported circling behavior and hyper reaction to touching in Dmp1 null mice. Our histology, tartrate resistant acid phosphatase (TRAP) staining and µCT data showed dramatic changes, such as an expansion of poorly mineralized matrices, in the Dmp1 null porous bony structure in the vestibular apparatus. The targeted re-expression of DMP1 in the Dmp1 null bone fully rescued not only the bone phenotype, but also circling behavior and hyper reaction. Furthermore, X-gal stain and DMP1 immunohistochemistry assay showed that DMP1 was not expressed in neuron cells or balance related cells in the inner ear, suggesting that a defect in the bony labyrinth of the internal ear is indirectly responsible for the circling behavior and/or hyper reaction to touching. Finally, discovery of DMP1 lacZ signal in pericyte-like cells may suggest a new function of DMP1 in angiogenesis.