A pair of ascending neurons in the subesophageal zone mediates aversive sensory inputs-evoked backward locomotion in Drosophila larvae.

Animals typically avoid unwanted situations with stereotyped escape behavior. For instance, Drosophila larvae often escape from aversive stimuli to the head, such as mechanical stimuli and blue light irradiation, by backward locomotion. Responses to these aversive stimuli are mediated by a variety of sensory neurons including mechanosensory class III da (C3da) sensory neurons and blue-light responsive class IV da (C4da) sensory neurons and Bolwig's organ (BO). How these distinct sensory pathways evoke backward locomotion at the circuit level is still incompletely understood. Here we show that a pair of cholinergic neurons in the subesophageal zone, designated AMBs, evoke robust backward locomotion upon optogenetic activation. Anatomical and functional analysis shows that AMBs act upstream of MDNs, the command-like neurons for backward locomotion. Further functional analysis indicates that AMBs preferentially convey aversive blue light information from C4da neurons to MDNs to elicit backward locomotion, whereas aversive information from BO converges on MDNs through AMB-independent pathways. We also found that, unlike in adult flies, MDNs are dispensable for the dead end-evoked backward locomotion in larvae. Our findings thus reveal the neural circuits by which two distinct blue light-sensing pathways converge on the command-like neurons to evoke robust backward locomotion, and suggest that distinct but partially redundant neural circuits including the command-like neurons might be utilized to drive backward locomotion in response to different sensory stimuli as well as in adults and larvae.

Comparing response blocking and response interruption/redirection on levels of motor stereotypy: Effects of data analysis procedures.

Autism spectrum disorder (ASD) is marked by deficits in social communication and the presence of restrictive and/or repetitive behaviors or interests. Motor stereotypy is a form of repetitive behavior that is common in ASD. Response Interruption and Redirection (RIRD) and response blocking (RB) are two interventions found to be efficacious in reducing motor stereotypy. However, the current literature presents with inconsistencies regarding the relative efficacy of these two procedures. Thus, we sought to replicate and extend previous literature by evaluating the efficacy of both interventions on reducing motor stereotypy among 3 individuals with ASD. We also sought to evaluate how variations in data analysis affected the interpretation of treatment outcomes. Results indicated that both interventions were equally efficacious at reducing stereotypy when analyzing data exclusive of treatment-implementation time. However, when analyzing total session time data, RB produced greater and more sustained reductions in stereotypy across all participants. These results emphasize the importance of data analysis decision-making in evaluating intervention outcomes.

Motor stereotypies and cognitive perseveration in non-human primates exposed to early gestational irradiation.

A number of psychiatric illnesses have been associated with prenatal disturbance of brain development, including autism, attention deficit hyperactivity disorder, and schizophrenia. Individuals afflicted with these disorders exhibit both repetitive motor and cognitive behavior. The potential role that environmental insult to the developing brain may play in generating these aberrant behaviors is unclear. Here we examine the behavioral consequences of an early gestational insult in the non-human primate. Rhesus macaques were exposed to x-irradiation during the first trimester of development to disrupt neurogenesis. The behavior of five fetally irradiated monkeys (FIMs) and five control monkeys (CONs) was observed as they matured from juvenile (1.5 years) to adult ages (4-5 years). Home-cage behavior was indistinguishable in the two groups. In the testing cage, circling was prevalent in both groups at juvenile ages, persisting to adulthood in three of the five FIMs. One FIM executed a ritualized motor sequence marked by semi-circling and undulating head movements. Seven macaques (4 FIMs, 3 CONs) were tested on a spatial Delayed Alternation (DA) task as adults. Perseverative errors and non-perseverative errors were recorded in early stages of the testing, at the 0 delay interval. While performing DA, FIMs made more errors of perseveration than CONs yet the number of total errors committed did not differ between groups. The presence of motor stereotypies and cognitive perseveration in fetally irradiated non-human primates suggests that environmental insult to the embryonic brain may contribute to repetitive motor and cognitive behaviors in neuropsychiatric diseases.

No todo es diversión: papiledema y montana rusa / Not everything is fun: papilledema and roller coaster

Presentamos el caso de una paciente de 30 años de edad previamente saludable, quien desarrolló luego de numerosos viajes en una montaña rusa un hematoma subdural espontáneo y un higroma contralateral. La estroma velocidad y despliegue de fuerza G, la sucesión de momentos de aceleración y desaceleración, los bruscos movimientos cefálicos con tironeo lateral del cerebro y el número de veces que permitió el viaje, constituyeron un riesgo significativo de ruptura de venas puente, siendo posible que las reiteradas caídas de una boya remolcada hayan constituido el último trauma y desencadenamiento final

We present the case of a 30-year-old previously healthy patient, who developed ofter numerous trips on a roller coaster a spontaneous hematoma subdural and a contralateral hygroma. Extreme speed and G-force deployment, the succession of moments of acceleration and deceleration, sudden cephalic movements with snarling side of the brain and the number of times that he repeated the trip, they constituted a significant risk of rupture of veins bridge, being possible that repeated falls from a towed buoy have produced the latest trauma and final trigger

Identification of nonvisual photomotor response cells in the vertebrate hindbrain.

Nonvisual photosensation enables animals to sense light without sight. However, the cellular and molecular mechanisms of nonvisual photobehaviors are poorly understood, especially in vertebrate animals. Here, we describe the photomotor response (PMR), a robust and reproducible series of motor behaviors in zebrafish that is elicited by visual wavelengths of light but does not require the eyes, pineal gland, or other canonical deep-brain photoreceptive organs. Unlike the relatively slow effects of canonical nonvisual pathways, motor circuits are strongly and quickly (seconds) recruited during the PMR behavior. We find that the hindbrain is both necessary and sufficient to drive these behaviors. Using in vivo calcium imaging, we identify a discrete set of neurons within the hindbrain whose responses to light mirror the PMR behavior. Pharmacological inhibition of the visual cycle blocks PMR behaviors, suggesting that opsin-based photoreceptors control this behavior. These data represent the first known light-sensing circuit in the vertebrate hindbrain.

Extremely low frequency magnetic field induced changes in motor behaviour of gerbils submitted to global cerebral ischemia.

The purpose of this study was to evaluate behavioural effects of an extremely low frequency magnetic field (ELF-MF) in 3-month-old Mongolian gerbils submitted to global cerebral ischemia. After 10-min occlusion of both common carotid arteries, the gerbils were placed in the vicinity of an electromagnet and continuously exposed to ELF-MF (50Hz, 0.5mT) for 7 days. Their behaviour (locomotion, stereotypy, rotations, and immobility) was monitored on days 1, 2, 4, 7, and 14 after reperfusion for 60min in the open field. It was shown that the 10-min global cerebral ischemia per se induced a significant motor activity increase (locomotion, stereotypy and rotations), and consequently immobility decrease until day 4 after reperfusion, compared to control gerbils. Exposure to ELF-MF inhibited development of ischemia-induced motor hyperactivity during the whole period of registration, but significantly in the first 2 days after reperfusion, when the postischemic hyperactivity was most evident. Motor activity of these gerbils was still significantly increased compared to control ones, but only on day 1 after reperfusion. Our results revealed that the applied ELF-MF (50Hz, 0.5mT) decreased motor hyperactivity induced by the 10-min global cerebral ischemia, via modulation of the processes that underlie this behavioural response.

High-frequency stimulation of the anterior subthalamic nucleus reduces stereotyped behaviors in primates.

Growing evidence shows that dysfunction of the limbic basal ganglia (BG) network is implicated in repetitive behaviors, such as obsessive compulsive disorder (OCD) and Tourette's syndrome (TS), in humans. Because deep brain stimulation (DBS) of the posterior subthalamic nucleus (STN), which modulates the sensorimotor BG network, is beneficial in movement disorders, stimulation of the anterior, limbic STN might improve intractable behavioral disorders. We therefore evaluated the effect of anterior STN stimulation on the repetitive behaviors induced in two monkeys after bicuculline-induced dysfunction of the limbic external globus pallidus. DBS in the anterior STN dramatically reduced the stereotypies, but had no effect on the performance of a simple food retrieval task. Stimulations outside the STN were less effective in reducing the stereotypies. Electrode trajectories, reconstructed postmortem, confirmed that the effective contacts were in the anterior STN. DBS in the limbic STN might therefore provide relief from the severe stereotyped behaviors observed in OCD and TS.

Different effects of chronic exposure to ELF magnetic field on spontaneous and amphetamine-induced locomotor and stereotypic activities in rats.

The effects of chronic (7 days) exposure to an extremely low frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) on spontaneous and amphetamine-induced (1.5mg/kg, i.p.) locomotor and stereotypic activities in adult rats were examined by open field test for 2h on exposure days 1, 3, and 7. After 1 day of exposure to ELF-MF, the spontaneous locomotor activity was increased clearly at the first hour of observation and significantly at the second one as compared to the corresponding values in other series with ELF-MF and sham-exposed animals. After 7 days of exposure to ELF-MF, an amphetamine enhancing effect on the locomotor activity was significantly reduced at the second hour of observation as compared to that in 1-day- and sham-exposed rats treated with amphetamine. In contrast to the locomotor activity, the amphetamine-induced stereotypic behaviour in 7-day pre-exposed rats was significantly reduced at the first hour versus sham-exposed rats. While at the second hour of observation this effect was significant as compared to 1- and 3-day exposed animals (but not sham-exposed rats). Our results indicate that an extremely low frequency magnetic field is able to affect differently two types of behaviour, which are dependent on both the time course of exposure and the imbalance in the brain mediatory systems.

The effect of extremely low-frequency magnetic field on motor activity of rats in the open field.

Exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) for seven days did not change spontaneous motor activity of rats in the open field compared to sham-exposed animals. Pre-exposure to ELF-MF decreased locomotor and stereotypic activity induced by amphetamine (1.5 mg/kg body weight) and accordingly increased the resting time compared to sham-exposed and amphetamine-treated rats. Vertical activity (rearing) of these two groups was similar. Our results indicate that ELF-MF has different effects on some parameters of amphetamine-induced motor activity, probably due to brain region-specific effects on catecholaminergic systems responsible for movement control.

Proximal cues of pocket gopher burrow plugging behavior: influence of light, burrow openings, and temperature.

Burrow plugging is readily observed among mammals adapted for digging (i.e., fossorial mammals) as they create and maintain their burrows. We investigated the influence of light, burrow openings, and thermal environment as cues of pocket gopher (Thomomys mazama, Thomomys talpoides) behavior. When given free access to light and no light during artificial-burrow preference trials, both Thomomys spp. consistently plugged (i.e., avoided) light treatments. Burrow openings did not notably affect plugging behavior of T. mazama. Gophers (T. talpoides) plugged the artificial burrows within the light and cold (7 degrees C) treatments, but not within the no-light, and 18 or 31 degrees C treatments when light and temperature were varied independently. Whereas the presence of light and low ambient temperatures induce burrow maintenance by pocket gophers, these cues help meliorate adverse conditions within subsurface environs.

Non-linearity in combined effects of ELF magnetic field and amphetamine on motor activity in rats.

The effects of short-term (15 min) pre-exposure of rats to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 6 mT) on their motor (locomotor and stereotypic) activity induced by d-amphetamine sulphate (AMPH) at different doses (0.5, 1.5 and 4.5mg/kg, i.p.) were studied in the open field test. In saline-treated rats both parameters of motor activity were unaffected by ELF-MF irradiation. The rats pre-exposed to ELF-MF and injected with the lowest dose of AMPH showed the same locomotor activity as control animals, while their stereotypic behaviour was significantly elevated. ELF-MF in combination with AMPH at higher doses significantly enhanced motor activity when compared with values obtained in both control and combined experiments with the lowest dose of the drug. However, only combined locomotor effect at the middle dose of AMPH was significantly greater than those observed in corresponding experiments with AMPH alone. These results demonstrate that acute short-term exposure to ELF-MF is able to modify a motor activity in dependence on the extent of AMPH-induced neurotransmitter imbalance.

Circling, deafness, and yellow coat displayed by yellow submarine (ysb) and light coat and circling (lcc) mice with mutations on chromosome 3.

We describe here two mouse mutants, yellow submarine (Ysb) and light coat and circling (Lcc). Ysb arose as the result of insertions of a transgene, pAA2, into the genome. Lcc is an independent, radiation-induced mutation. Both mutants are characterized by recessive circling behavior and deafness, associated with a non-segregating, semi-dominant yellow coat color. Complementation tests showed that Ysb and Lcc are allelic. We attribute the yellow coat in Ysb and Lcc mice to the absence of black awl overhairs, increased agouti zigzag underhairs, and the presence of agouti awls with long subapical yellow pigment. Chromosomal mapping and genomic characterization showed the Ysb and Lcc mutations involve complex chromosomal rearrangements in overlapping regions of mouse chromosome 3, A2/A3-B/C and B-E1, respectively. Ysb and Lcc show for the first time, to our knowledge, the presence of genes in the B-C region of chromosome 3 important for balance and hearing and the pigmentation and specification of coat hair.

Effects of prenatal exposure to gamma rays on circling and activity behavior in prepubertal and postpubertal rats.

The study departs from the finding that postural asymmetries in low-weight female neonates are greatly increased following prenatal lesions inflicted by gamma irradiation at day 15. Given that amphetamine-induced rotation in adult rats could be predicted by their infantile axial asymmetry we expected a greater tendency for circling in rats exposed at day 15. To examine this prediction, Sprague-Dawley rats were exposed to a single dose of gamma radiation at 1.5 Gy with a dose-rate of 0.15 Gy/min. The dose was delivered on one of the embryonic days (E15, 17 or 19) throughout the whole body of pregnant dams. Sham prenatal exposure of controls consisted of placing pregnant rats in the same environment for 10 min. All rats were tested during the active part of the circadian cycle. At postnatal day 27 (P27) exposed pups did not differ in rates of either spontaneous or d-amphetamine-induced circling from the shams. At P57, in keeping with our prediction, E15 rats manifested enhanced rotation and higher net asymmetry. However, E17 also showed higher gyration tendency compared to their shams while exposed E19 rats did not differ from their shams. The role of intrinsic DAergic imbalance presumably sharpened by irradiation at E15 and of neocortical deficit inflicted at E15 and E17 are discussed.

Effects of prenatal ultrasound exposure on adult offspring behavior in the Wistar rat.

An ultrasound exposure tank was specifically designed for experimental bioeffects studies. Thirty-six pregnant rats were anesthetized, immersed to the axilla in a water tank, and exposed on Day 15, 17, and 19 of gestation. Twelve rats were exposed to 5.0 MHz pulsed ultrasound of effective pulse duration equal to approximately 0.170 microseconds, pulse repetition rate (PRF) 1 kHz, and a spatial peak, temporal peak intensity (lsptp) of 500 W/cm2, representing a clinically appropriate exposure level. The spatial peak pulse average (lsppa), spatial peak temporal average (lspta), and instantaneous maximum (lm) intensities were determined to be 100 W/cm2, 24 mW/cm2, and 230 W/cm2, respectively. The maximum rarefraction pressure, pr, was measured as 12.5 x 10(5) Pa, and the total power was 2.5 mW. Twelve other rats were exposed to 1500 W/cm2, lsptp, and 12 were sham insonified. Since the focal area was about 0.05 cm2, computer controlled stepper motors moved the rats through the ultrasound field to ensure uniform exposure of the abdominal/pelvic region. Total exposure time was 35 min. A miniature thermocouple was implanted in a few rats to verify that no significant temperature increase took place due to exposure. A total of 278 offspring were maintained until postnatal Day 60 when they were subjected to two of four behavioral tests in random order within sexes. The results indicate no consistently observed dose-related alterations in adult behavior due to prenatal fetal exposure to 5.0 MHz ultrasound below an intensity (lsptp) of 1500 W/cm2.

Early neural grafts transiently reduce the behavioral effects of radiation-induced fascia dentata granule cell hypoplasia.

X-irradiation of the neonatal rat hippocampus produces a selective hypoplasia of fascia dentata granule cells, locomotor hyperactivity, perseverative movements and deficits in passive avoidance. We previously reported that transplantation of fetal hippocampal tissue into the adult (age = 182 +/- 4 days) brain produced a partial recovery of these behavioral deficits. Since graft/host interconnections are more prominent when transplants are conducted soon after radiation-induced hippocampal damage, in this study we transplanted hippocampal or cerebral cortex neurons when host rats were 33 +/- 5 days of age (i.e. only 16 days after radiogenic brain damage). Behavioral evaluations were conducted 80 and 182 days after transplantation or surgical control procedures. In the first test series only, selective components of locomotion (e.g. stereotypy and total distance traveled) and perseverative turning (e.g. mean bout length and turning speed topography) were normalized by the hippocampal grafts. Radiation-induced changes in passive avoidance were less prominent in these studies than in past experiments. Still, transplantation of hippocampal tissue improved performance on this learning task as well. Cerebral cortex grafts did not produce reliable improvements in most behavioral measures. These data suggest that hippocampal grafts placed soon after X-ray induced fascia dentata hypoplasia reduce a broad range of behavioral deficits. However, these benefits are transient and, for the most part, depend on the use of transplant tissues homologous with those damaged.

Spontaneous perseverative turning in rats with radiation-induced hippocampal damage.

This study found a new behavioral correlate of lesions specific to the dentate granule cell layer of the hippocampus: spontaneous perseverative turning. Irradiation of a portion of the neonatal rat cerebral hemispheres produced hypoplasia of the granule cell layer of the hippocampal dentate gyrus while sparing the rest of the brain. Radiation-induced damage to the hippocampal formation caused rats placed in bowls to spontaneously turn in long, slow bouts without reversals. Irradiated subjects also exhibited other behaviors characteristic of hippocampal damage (e.g., perseveration in spontaneous exploration of the arms of a T-maze, retarded acquisition of a passive avoidance task, and increased horizontal locomotion). These data extend previously reported behavioral correlates of fascia dentata lesions and suggest the usefulness of a bout analysis of spontaneous bowl turning as a measure of nondiscrete-trial spontaneous alternation and a sensitive additional indicator of radiation-induced hippocampal damage.

Microwave facilitation of domperidone antagonism of apomorphine-induced stereotypic climbing in mice.

The dopaminergic agonist apomorphine produced dose-dependent stereotypic climbing behavior in mice housed in cages with vertical bars. This drug effect was competitively inhibited by systemic pretreatment with the centrally acting dopaminergic antagonist haloperidol but not by microwave irradiation (2.45 GHz, 20 mW/cm2, CW, 10 min) nor by systemic pretreatment with domperidone, a dopaminergic antagonist that only poorly penetrates the blood-brain barrier (BBB). Yet when mice were systemically pretreated with domperidone and then subjected to microwave irradiation (as above), the apomorphine effect was significantly reduced. Microwave irradiation also facilitated antagonism of the apomorphine effect by low and otherwise ineffective systemic pretreatment doses of haloperidol. Apomorphine-induced stereotypic climbing behavior was also reduced by domperidone administered intracerebrally, which bypassed the BBB. Exposure of intracerebral domperidone-pretreated animals to microwave irradiation failed to increase the degree of antagonism. These findings indicate that microwave irradiation can facilitate central effects of domperidone, a drug which acts mainly in the periphery. One possible explanation for these findings is that microwave irradiation alters the permeability of the BBB and increases the entry of domperidone to central sites of action.