Circling Behavior Research Articles

Look, no ears: waltzing without balance

Information about head movement and orientation, from the semicircular canals and otolith organs of the inner ear, is essential for the normal control of eye movements, gaze and body posture, as well as cognitive orientation and spatial navigation. Increasingly it also appears that vestibular sensory inputs play an important role in the early postnatal development of normal motor control. Thus, in human infants with congenital lack of labyrinthine function there is a marked slowing of motor development (Kaga, 1999), while many mouse mutants with inner ear deformities show a characteristic, life-long head bobbing and rapid circling behaviour (the shaker/waltzer phenotype; Rabbath et al. 2001; Vidal et al. 2004). The role of vestibular inputs in shaping the early development of motor systems is largely unexplored. In this volume of The Journal of Physiology, Eugène et al. (2007) show that vestibular information may have an essential, formative role in the development of the motor system at an early age. Eugène et al. (2007) exploited a transgenic mouse strain with a null mutation of the KCNE1 gene, encoding the IsK channel protein, which causes a complete loss of sensory hair cells in the inner ears soon after birth (Vetter et al. 1996, Vidal et al. 2004). The KCNE1−/− animal shows characteristic signs of severe vestibular loss as early as postnatal day 7 (head bobbing, circling, inability to swim, difficulty in righting). Since KCNE1 is not expressed in the brain, this mutant provides a useful model in which the peripheral sensory receptors degenerate while the central vestibular pathways, presumably, are normal. In a previous behavioural analysis also published in The Journal of Physiology, Vidal et al. (2004) showed that the resting posture of the KCNE1−/− mouse was normal, but its locomotion was characterized by circling episodes to either side, so that the mutant animal could not walk in a straight line. Thus, proprioceptive inputs may help compensate for the lack of vestibular feedback in the regulation of posture, but the vestibular system appears to be essential for normal walking. In the current study, Eugène et al. (2007) analysed in detail the intrinsic membrane and firing properties of neurons in the medial vestibular nucleus (MVN) of the KCNE1−/− mouse. Remarkably, in the adult mutant mouse the membrane properties and firing rates of MVN neurons are very similar to normal. The head bobbing and waltzing behaviour is therefore not due to deficits at the level of the brainstem vestibular networks. Instead, the KCNE1−/− animal is equivalent to a bilaterally labyrinthectomised, normal animal – it receives no afferent inputs from the two inner ears, and its vestibular neurons are essentially normal. Crucially, however, much previous research has shown that bilateral labyrinthectomy in adult, normal animals never induces the characteristic head bobbing and waltzing behaviour seen in the mutant. Eugène et al. therefore conclude that the head instability and waltzing behaviour is precipitated only if the vestibular information is absent at some critical, early stage in postnatal life. Perhaps the vestibular signals relating to gravity, orientation and self-motion are essential for the correct postnatal maturation of forebrain motor circuits, particularly in the basal ganglia. Disorders of motor function may therefore result either from a congenital lack of vestibular information during this critical period, as observed in many mouse mutant strains with inner ear malformations, or alternatively in mutants where the inner ears are normal, because of basal ganglia deficits that prevent this information being correctly used. Further studies of the effects of early vestibular deprivation on motor development in the mouse, and the identification of their human equivalents, promise to be interesting.

Modulation of the motor response to dopaminergic drugs in a parkinsonian model of combined dopaminergic and noradrenergic degeneration

Besides dopaminergic deficiency, other neurotransmitter systems such as noradrenergic nuclei are affected in Parkinson's disease. Locus coeruleus degeneration might influence the response to dopamine replacement and the presence of long-term complications such as dyskinesias. In this scenario of noradrenergic and dopaminergic neurodegeneration, behavioural effects induced by dopaminergic-interacting drugs are incompletely known. We investigated whether noradrenergic lesion modulates the levodopa ( l-DOPA) response and modifies the response to adenosine antagonists and its interaction with l-DOPA. We examined the motor behaviour induced by: 1) subthreshold doses of l-DOPA (2mg/kg, i.p.), 2) the adenosine-receptor antagonist caffeine (10mg/kg), and 3) the combination of l-DOPA (2mg/kg) and caffeine (10mg/kg). Each study was done in two experimental conditions: a) rats with unilateral 6-OHDA lesion and b) rats with a lesion of the nigrostriatal pathway (6-OHDA) combined with selective denervation of locus coeruleus-noradrenergic terminal fields by N-(2-chloroethyl)- N-ethyl-2-bromobenzylamine (DSP-4). While only 28% of the 6-OHDA-lesioned animals presented circling behaviour after l-DOPA challenge, all (100%) double-denervated animals rotated after the same l-DOPA dose ( p < 0.05). No statistical differences in the percentage of rotating animals were observed between single- and double-denervated rats after caffeine challenge. Combined l-DOPA–caffeine challenge produced rotational behaviour in all (100%) single- and double-denervated rats. No differences in total turns were observed between single- and double-denervated animals in each treatment condition. These findings suggest that additional noradrenergic denervation selectively decreases the motor threshold to l-DOPA treatment without modifying the magnitude or the pattern of the motor response to adenosinergic antagonism.

Defects in vestibular sensory epithelia and innervation in mice with loss of Chd7 function: Implications for human CHARGE syndrome

CHD7 is a chromodomain gene mutated in CHARGE syndrome, a multiple anomaly condition characterized by ocular coloboma, heart defects, atresia of the choanae, retarded growth and development, genital hypoplasia, and ear defects including deafness and semicircular canal dysgenesis. Mice with heterozygous Chd7 deficiency have circling behavior and semicircular canal defects and are an excellent animal model for exploring the pathogenesis of CHARGE features. Inner ear vestibular defects have been characterized in heterozygous Chd7-deficient embryos and early postnatal mice, but it is not known whether vestibular defects persist throughout adulthood in Chd7-deficient mice or whether the vestibular sensory epithelia and their associated innervation and function are intact. Here we describe a detailed analysis of inner ear vestibular structures in mature mice that are heterozygous for a Chd7-deficient, gene-trapped allele (Chd7(Gt/+)). Chd7(Gt/+) mice display variable asymmetric lateral and posterior semicircular canal malformations, as well as defects in vestibular sensory epithelial innervation despite the presence of intact hair cells in the target organs. These observations have important functional implications for understanding the clinical manifestations of CHD7 mutations in humans and for designing therapies to treat inner ear vestibular dysfunction.

Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats

Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 microl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid.

Whirler Mutant Hair Cells Have Less Severe Pathology than Shaker 2 or Double Mutants

MYOSIN XV is a motor protein that interacts with the PDZ domain-containing protein WHIRLIN and transports WHIRLIN to the tips of the stereocilia. Shaker 2 (sh2) mice have a mutation in the motor domain of MYOSIN XV and exhibit congenital deafness and circling behavior, probably because of abnormally short stereocilia. Whirler (wi) mice have a similar phenotype caused by a deletion in the third PDZ domain of WHIRLIN. We compared the morphology of Whrn (wi/wi) and Myo15 (sh2/sh2) sensory hair cells and found that Myo15 (sh2/sh2) have more frequent pathology at the base of inner hair cells than Whrn (wi/wi), and shorter outer hair cell stereocilia. Considering the functional and morphologic similarities in the phenotypes caused by mutations in Myo15 and Whrn, and the physical interaction between their encoded proteins, we used a genetic approach to test for functional overlap. Double heterozygotes (Myo15 (sh2/+), Whrn (wi/+)) have normal hearing and no increase in hearing loss compared to normal littermates. Single and double mutants (Myo15 (sh2/sh2), Whrn (wi/wi)) exhibit abnormal persistence of kinocilia and microvilli, and develop abnormal cytoskeletal architecture. Double mutants are also similar to the single mutants in viability, circling behavior, and lack of a Preyer reflex. The morphology of cochlear hair cell stereocilia in double mutants reflects a dominance of the more severe Myo15 (sh2/sh2) phenotype over the Whrn (wi/wi) phenotype. This suggests that MYOSIN XV may interact with other proteins besides WHIRLIN that are important for hair cell maturation.

The corticotrophin‐releasing factor‐like peptide urocortin reverses key deficits in two rodent models of Parkinson's disease

The potential neuroprotective action of the corticotrophin-releasing factor-related peptide urocortin (UCN) was investigated in the rat 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS) paradigms of Parkinson's disease. UCN (20 fmol) was either given at the same time as (T = 0) or 7 days after (T = +7) intracerebral 6-OHDA or LPS injection. At 14 days after 6-OHDA or LPS injection, circling behaviour was measured following apomorphine challenge. Circling was significantly lower in rats given UCN at either T = 0 or T = +7 compared with animals given 6-OHDA or LPS and vehicle. Sham-treated rats showed no circling. Consistent with these observations, striatal dopamine concentrations were markedly higher in 6-OHDA/LPS + UCN rats vs. 6-OHDA/LPS + vehicle groups. Additionally, L-dihydroxyphenylalanine production by tyrosine hydroxylase was greatly reduced in the striata of 6-OHDA/LPS + vehicle rats, whereas this was not the case in rats coadministered UCN. Finally, the numbers of tyrosine hydroxylase-positive cells recorded in the substantia nigra of 6-OHDA/LPS + vehicle-treated animals were markedly lower than those of sham-operated or 6-OHDA/LPS + UCN rats. Critically, UCN was effective in reversing lesion-induced deficits when given either at the same time as or 7 days after the neurotoxic insult. To our knowledge, this is the first time that such an effect has been demonstrated in vivo. The apparent ability of UCN to arrest the progression of or even reverse nigral lesions once established suggests that pharmacological manipulation of this system could have substantial therapeutic utility.

Mutational spectrum ofMYO15A: the large N-terminal extension of myosin XVA is required for hearing

Human MYO15A is located on chromosome 17p11.2, has 66 exons and encodes unconventional myosin XVA. Recessive mutations of MYO15A are associated with profound, nonsyndromic hearing loss DFNB3 in humans, and deafness and circling behavior in shaker 2 mice. In the inner ear, this motor protein is necessary for the development of hair cell stereocilia, which are actin-filled projections on the apical surface and the site of mechanotransduction of sound. The longest isoform of myosin XVA has 3,530 amino acid residues. Two isoform classes of MYO15A are distinguished by the presence or absence of 1,203 residues preceding the motor domain encoded by alternatively-spliced exon 2. It is not known whether this large N-terminal extension of myosin XVA is functionally necessary for hearing. We ascertained approximately 600 consanguineous families segregating hereditary hearing loss as a recessive trait and found evidence of linkage of markers at the DFNB3 locus to hearing loss in 38 of these families ascertained in Pakistan (n=30), India (n=6), and Turkey (n=2). In this study, we describe 16 novel recessive mutations of MYO15A associated with severe to profound hearing loss segregating in 20 of these DFNB3-linked families. Importantly, two homozygous mutant alleles-c.3313G>T (p.E1105X) and c.3334delG (p.G1112fsX1124) of MYO15A-located in exon 2 are associated with severe to profound hearing loss segregating in two families. These data demonstrate that isoform 1, containing the large N-terminal extension, is also necessary for normal hearing.

Overexpression of D2/D3 receptors increases efficacy of ropinirole in chronically 6-OHDA-lesioned Parkinsonian rats

Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague–Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 h) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD.

The chemokine stromal cell‐derived factor‐1/CXCL12 activates the nigrostriatal dopamine system

We recently demonstrated that dopaminergic (DA) neurons of the rat substantia nigra constitutively expressed CXCR4, receptor for the chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 (SDF-1). To check the physiological relevance of such anatomical observation, in vitro and in vivo approaches were used. Patch clamp recording of DA neurons in rat substantia nigra slices revealed that SDF-1 (10 nmol/L) induced: (i) a depolarization and increased action potential frequency; and (ii) switched the firing pattern of depolarized DA neurons from a tonic to a burst firing mode. This suggests that SDF-1 could increase DA release from neurons. Consistent with this hypothesis, unilateral intranigral injection of SDF-1 (50 ng) in freely moving rat decreased DA content and increased extracellular concentrations of DA and metabolites in the ipsilateral dorsal striatum, as shown using microdialysis. Furthermore, intranigral SDF-1 injection induced a contralateral circling behavior. These effects of SDF-1 were mediated via CXCR4 as they were abrogated by administration of a selective CXCR4 antagonist. Altogether, these data demonstrate that SDF-1, via CXCR4, activates nigrostriatal DA transmission. They show that the central functions of chemokines are not restricted, as originally thought, to neuroinflammation, but extend to neuromodulatory actions on well-defined neuronal circuits in non-pathological conditions.

Comparative analysis of anxiety-like behaviors and sensorimotor functions in two rat mutants, ci2 and ci3, with lateralized rotational behavior

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 ci2 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.

Marked differences in response to dopamine receptor antagonism in two rat mutants, ci2 and ci3, with lateralized rotational behavior

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.

Gamma Knife Radiosurgery Targeting Protocols for the Experiments with Small Animals

Background/Aims: Manipulation of brain functions via Gamma Knife (GK) irradiation would have numerous applications in clinical and experimental neurology. Methods: Alteration of brain functions in the unilaterally irradiated striatum was indexed through monitoring freely moving rat behaviors. Spontaneous activity and rotations on the apomorphine test, which can detect dopaminergic function imbalance, were indexed employing our behavior tracking system. The spatial distribution of necrotic lesions was explored using serial sections, and was assumed to represent the real foci of the GK target. Results: Distinct behavioral alterations corresponded to the precise locations of the lesions in various areas of the basal ganglia. Displacement of the irradiation sites in the anteromedial direction increased spontaneous activity, and posterolateral shift provoked circling behavior on the apomorphine test. Conclusion: Accurate positioning of the target is crucial for experimental GK irradiation locally focused on domains of a small brain such as that of the rat. Here, we propose a protocol for converting the ‘intended’ focus, based on brain map coordinates, to a ‘planned’ focus on the MR imaging coordinate system with the Régis-Valliccioni stereotactic frame.

STEREOTYPIC CIRCLING BEHAVIOR IN MICE WITH VESTIBULAR DYSFUNCTION: ASYMMETRICAL EFFECTS OF INTRASTRIATAL MICROINJECTION OF A DOPAMINE AGONIST

Bronx Waltzer (bv) mouse, which has been used as a model of hearing and vestibular dysfunction, shows remarkable repetitive circling behavior. This study investigated whether the behavior is caused by the asymmetry of striatal function by observing the behavior of the bv mice following microinjection of dopamine D1 agonist, A68930 into the striatum ipsilaterally and contralaterally to the preferred direction of rotation separately. High dose of the drug induced opposite effects on ipsilateral rotations by the side of injections with statistical significance (p = .0026). These results suggested that the stereotypic circling behavior involves striatum and is based on striatal asymmetry.

The role of bone morphogenetic protein 4 in inner ear development and function

Bone Morphogenetic Protein 4 (BMP4) is a member of the TGF- β superfamily and is known to be important for the normal development of many tissues and organs, including the inner ear. Bmp4 homozygous null mice die as embryos, but Bmp4 heterozygous null ( Bmp4 +/−) mice are viable and some adults exhibit a circling phenotype, suggestive of an inner ear defect. To understand the role of BMP4 in inner ear development and function, we have begun to study C57BL/6 Bmp4 +/− mice. Quantitative testing of the vestibulo-collic reflex, which helps maintain head stability, demonstrated that Bmp4 +/− mice that exhibit circling behavior have a poor response in the yaw axis, consistent with semicircular canal dysfunction. Although the hair cells of the ampullae were grossly normal, the stereocilia were greatly reduced in number. Auditory brainstem responses showed that Bmp4 +/− mice have elevated hearing thresholds and immunohistochemical staining demonstrated decreased numbers of neuronal processes in the organ of Corti. Thus Bmp4 +/− mice have structural and functional deficits in the inner ear.

Alterations in dopamine D3 receptors in the circling ( ci3) rat mutant

We have previously described a black-hooded mutant rat (BH.7A/Ztm- ci3/ci3) that displays abnormal lateralized circling behavior, but normal auditory and vestibular functions. Neurochemical determination of dopamine and dopamine metabolite levels in striatum, nucleus accumbens and substantia nigra showed that ci3 rats have a significant asymmetry in striatal dopamine in that dopamine levels were significantly lower in the hemisphere contralateral to the preferred direction of turning. Consistent with this finding, immunohistological examination of dopaminergic neurons in substantia nigra and ventral tegmental area yielded a significant laterality in the medial part of substantia nigra pars compacta with a lower density of tyrosine hydroxylase-positive neurons in the contralateral hemisphere of mutant circling rats, while no laterality was seen in unaffected rats of the background strain. In the present study, quantitative autoradiography was used to examine the binding of [ 3H]SCH 23390, [ 3H]raclopride and [ 3H]7-OH-DPAT (7-hydroxy-N,N-di-n-propyl-2-aminotetralin) to dopamine D1, D2, and D3 receptors, respectively, in various brain regions of ci3 rats and unaffected rats of the background strain (BH.7A(LEW)/Won). No significant differences between circling rats and controls were obtained for D1 and D2 receptor binding in any region, but mutant rats differed from controls in dopamine D3 binding in several regions. A significant decrease in D3 binding was seen in the shell of the nucleus accumbens, the islands of Calleja, and the subependymal zone of ci3 mutant rats. Furthermore, a significant laterality in D3 binding was determined in ci3 rats in that binding was lower in the contralateral hemisphere in the shell of the nucleus accumbens and the islands of Calleja. Our data indicate that alterations of dopamine D3 receptors may be involved in the behavioral phenotype of the ci3 rat, thus substantiating the findings from a recent genetic linkage analysis that indicated the D3 receptor gene as a candidate gene in this rat mutant.

Ush1c216A knock-in mouse survives Katrina

Usher syndrome is the most common cause of inherited deafness found in combination with blindness. All Usher patients suffer progressive retinitis pigmentosa, with the degree of hearing impairment and the presence or absence of vestibular function differing among subtypes. A cryptic splice site mutation (216G → A) in exon 3 of the USH1C gene on chromosome 11p, which encodes a PDZ-domain protein, harmonin, was found in Acadian Usher type IC patients in south Louisiana. In vitro analysis using constructs containing the mutant 216A and subsequent analysis of patient cell lines revealed a deletion of 35 bases in the transcript. In order to analyze the impact of this frame-shift mutation, we created a knock-in mouse model containing the human 216G → A mutation. A targeting construct was made containing 5′ and 3′ homology arms, each 4 kb in length, and a 650 base pair fragment containing exons 3 and 4 of human USH1C cloned from an Acadian patient homozygous for the 216A mutation. W4/129S6 embryonic stem (ES) cells were electroporated with the targeting construct, and after 10 days of neomycin selection, clones were picked and screened by polymerase chain reaction (PCR) and Southern blot analysis for homologous recombination. Two positive clones for targeted insertion were microinjected into C57BL/6 blastocysts which were then transplanted into pseudo-pregnant females. Chimeras were bred with Cre recombinase-expressing mice for simultaneous deletion of the neomycin gene and germline transmission of the 216A allele. Homozygous Ush1c216A (216AA) mice are hyperactive, display circling and head tossing behavior, and do not have a Preyer reflex at 21–25 days old. RT-PCR analysis of the cochlea and retina from 216AA mice shows the same 35 base deletion characteristic of Usher IC patients.

Roller Coaster Behavior in the Cruziana Rugosa Group from Penha Garcia (Portugal): Implications for the Feeding Program of Trilobites

Trilobite burrows of the Cruziana rugosa group are common and well preserved in the Armorican Quartzite Formation (Lower to Middle Ordovician) of the Ponsul River gorge in Penha Garcia. Based on morphological and behavioral peculiarities, Cruziana beirensis is reinstated herein and included in the rugosa group. Apart from the broad range in morphology and size, Cruziana from Penha Garcia show higher behavioral diversity using food sources than has ever been documented in a single section. This behavioral diversity, mainly in circling behavior, has been analyzed using the Capacity Fractal Dimension by implementation of the box-counting theorem applied to the bedding plane. Fractal Dimension also suggests that Cruziana rouaulti can be included in the rugosa group, despite the obscurity of the scratch patterns, as products of juveniles. Circling, sinusoidal or teichichnoid behavior modifications reflect a generalist mode of sediment feeding, claimed mudtrophobacterivory, while most of the interactions with worm burrows originated previously or (mostly) later, by interpreted trilobite necrophagy and/or worm commensalism. Patchy exploitation of biomat grazing fields is inferred from Cruziana preservation styles, physical interactions with biomat-related sedimentary structures and area-limited high bioturbational indices in the explored tier.

Reproductive behaviour and early development in yellowtail kingfish ( Seriola lalandi Valenciennes 1833)

The spawning behaviour of wild caught brood stock as well as early egg and larval development were studied in yellowtail kingfish ( Seriola lalandi). Spawning occurred naturally in the austral spring/summer (November–February) when the seawater temperature was above 17 °C. Courtship behaviour involved one male and female, and consisted of a high-speed pursuit punctuated by stalling, nipping and touching. This lasted for approximately 0.5–1.5 h until, immediately prior to spawning, the male would nip at the female gonoduct, presumably to induce spawning. At this stage, in 50% of spawns, a second male would become involved. The release of gametes involved frenzied circling behaviour near the bottom of the tank and lasted approximately 22 s. Spawning occurred in the early daylight hours at the start of the spawning season, but shifted to around dusk in the latter part. Spawned eggs were positively buoyant, had a high fertilisation rate (> 99%), ranged 1.33–1.50 mm in diameter with a single oil droplet 0.30–0.33 mm diameter, and developed in a similar manner to that described in congenerics. Egg viability within the floating fraction was visually determined to be 74% ± 17% over the entire reproductive season. Indistinct cell margins and asymmetrical cleavage were the most common blastomere deformities observed. Egg and oil droplet volume were found to decrease by 15–20% over the spawning season, though no relationship was found between visually assessed egg viability and date. Egg incubation trials between 16 and 24 °C indicated that temperature accelerated the time to hatch by a Q 10 of 5.0. While larvae were found to hatch at a smaller length with a larger yolk sac and oil droplet at warmer incubation temperatures, there was little difference in the maximum larval length reached at the onset of first feeding among the rearing temperatures used. It is proposed that the reason for this was that higher incubation temperatures accelerated the hatching process faster than the rate of tissue deposition. The findings from this study are discussed in terms of the biological significance and implications for the larviculture of this species.

Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler ( jc) mutant mouse

Jackson circler ( jc) is a spontaneous, recessive mouse mutation that results in circling behavior and an impaired acoustic startle response. In this study, we refined the phenotypic and genetic parameters of the original jc mutation and characterized a new mutant allele, jc 2 J . In open-field behavior tests, homozygous jc mutants exhibited abnormal circling and ambulatory behavior that was indistinguishable from that of phenotypically similar mutants with defects in the vestibule of the inner ear. The jc/jc and jc 2 J / jc 2 J mice had stable elevated auditory-evoked brainstem response (ABR) thresholds at the 16 kHz stimulus of 88 ± 9 dB sound pressure levels (SPL) and 43 ± 11 dB SPL, respectively. Peak latencies and peak time intervals were normal in jc mutants. The jc mice showed no measurable distortion-product otoacoustic emissions (DPOAEs) above the system noise floor. In the mutant cochlea, the apical turn failed to form due to the developmental growth arrest of the cochlear duct at the level of the first turn at gestational day 13.5. In a large intrasubspecific intercross, jc localized to a 0.2cM interval at position 25cM on chromosome 10, which is homologous to the human 6q21 region. On CZECHII/Ei and CAST/Ei backgrounds jc/ jc mutant hearing thresholds at the 16 kHz stimulus were significantly lower than those observed on the C57BL/6J background, with means of 62 ± 22 dB SPL and 55 ± 18 dB SPL, respectively. Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects.

Patterns of cyprinid migration through a fishway in relation to light, water temperature and fish circling behaviour

Patterns of cyprinid migration were studied in a fishway located at a lock on the Elbe River, Czech Republic, weekly from spring to fall 2003. 24 hrs observations of fish were made with a Riverwatcher Fishcounter manufactured by Vaki (Iceland). The counter records revealed distinct diel patterns of migration. During spring, fish migrated mostly during the light part of a day, in summer and fall this pattern changed. Water temperature and illumination intensity were found as the major driving forces initiating spawning migration and controlling its development and diel pattern. This hypothesis was verified by significant influence of interaction of weather and atmospheric pressure on the number of migrating fish. Because circling of fish within a pool and between adjacent pools of the fishway was a common behavioural pattern, overestimates offish migration acitivity occurred, especially in the downstream direction. These results point out that circling behaviour and the effect of weather condition on fish migration should be taken into account in every fishway monitoring effort.