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Spatial and nonspatial escape strategies in the Barnes maze.

The Barnes maze is a spatial memory task that requires subjects to learn the position of a hole that can be used to escape the brightly lit, open surface of the maze. Two experiments assessed the relative importance of spatial (extra-maze) versus proximal visible cues in solving the maze. In Experiment 1, four groups of mice were trained either with or without a discrete visible cue marking the location of the escape hole, which was either in a fixed or variable location across trials. In Experiment 2, all mice were trained with the discrete visible cue marking the target hole location. Two groups were identical to the cued-target groups from Experiment 1, with either fixed or variable escape locations. For these mice, the discrete cue either was the sole predictor of the target location or was perfectly confounded with the spatial extra-maze cues. The third group also used a cued variable target, but a curtain was drawn around the maze to prevent the use of spatial cues to guide navigation. Probe trials with all escape holes blocked were conducted to dissociate the use of spatial and discrete proximal cues. We conclude that the Barnes maze can be solved efficiently using spatial, visual cue, or serial-search strategies. However, mice showed a strong preference for using the distal room cues, even when a discrete visible cue clearly marked the escape location. Importantly, these data show that the cued-target control version of the Barnes maze as typically conducted does not dissociate spatial from nonspatial abilities.

Analysis of Variance↗

Evidence for a widespread brain stem escape network in larval zebrafish.

Zebrafish escape behaviors, which typically consist of a C bend, a counter-turn, and a bout of rapid swimming, are initiated by firing of the Mauthner cell and two segmental homologs. However, after laser-ablation of the Mauthner cell and its homologs, escape-like behaviors still occur, albeit at a much longer latency. This might suggest that additional neurons contribute to this behavior. We therefore recorded the activity of other descending neurons in the brain stem using confocal imaging of cells retrogradely labeled with fluorescent calcium indicators. A large majority of identified descending neurons present in the larval zebrafish, including both ipsilaterally and contralaterally projecting reticulospinal neurons, as well as neurons from the nucleus of the medial longitudinal fasciculus, showed short-latency calcium responses after gentle taps to the head of the larva-a stimulus that reliably evokes an escape behavior. Previous studies had associated such in vivo calcium responses with the firing of action potentials, and because all responding cells have axons projecting into to spinal cord, this suggests that these cells are relaying escape-related information to spinal cord. Other identified neurons failed to show consistent calcium responses to escape-eliciting stimuli. In conjunction with previous lesion studies, these results indicate that the neural control systems for turning and swimming behaviors are widely distributed in the larval zebrafish brain stem. The degree of robustness or redundancy of this system has implications for the descending control of vertebrate locomotion.

Action Potentials↗

Escape manoeuvres in the spiny dogfish (Squalus acanthias).

The locomotor performance of dogfish during escape responses was observed by means of high-speed video. Dogfish show C-type escape responses that are comparable with those shown previously in teleosts. Dogfish show high variability of turning rates of the anterior part of the body (head to centre of mass), i.e. with peak values from 434 to 1023 deg. s(-1). We suggest that this variability may be due to the presence of two types of escape manoeuvres, i.e. responses with high and low turning rates, as previously found in a teleost species. Fast responses (i.e. with high maximum turning rates, ranging between 766 and 1023 deg. s(-1)) showed significantly higher locomotor performance than slow responses (i.e. with low maximum turning rates, ranging between 434 and 593 deg. s(-1)) in terms of distance covered, speed and acceleration, although no differences were found in the turning radius of the centre of mass during the escape manoeuvres. The existence of two types of escape responses would have implications in terms of both neural control and muscular activation patterns. When compared with literature data for the locomotor performance of bony fishes, dogfish showed relatively low speed and acceleration, comparable turning rates and a turning radius that is in the low part of the range when compared with teleosts, indicating relatively high manoeuvrability. The locomotor performance observed in dogfish is consistent with their morphological characteristics: (1) low locomotor performance associated with low thrust developed by their relatively small posterior depth of section and (2) relatively high manoeuvrability associated with their high flexibility.

Acceleration↗

Effects of temperature on escape jetting in the squid Loligo opalescens.

In Loligo opalescens, a sudden visual stimulus (flash) elicits a stereotyped, short-latency escape response that is controlled primarily by the giant axon system at 15 C. We used this startle response as an assay to examine the effects of acute temperature changes down to 6 C on behavioral and physiological aspects of escape jetting. In free-swimming squid, latency, distance traveled and peak velocity for single escape jets all increased as temperature decreased. In restrained squid, intra-mantle pressure transients during escape jets increased in latency, duration and amplitude at low temperature. Recordings of stellar nerve activity revealed repetitive firing of the giant motor axon accompanied by increased activity in the non-giant motor axons that run in parallel. Selective stimulation of giant and non-giant motor axons in isolated nerve-muscle preparations failed to show the effects seen in vivo, i.e. increased peak force and increased neural activity at low temperature. Taken together, these results suggest that L. opalescens is able to compensate escape jetting performance for the effects of acute temperature reduction. A major portion of this compensation appears to occur in the central nervous system and involves alterations in the recruitment pattern of both the giant and non-giant axon systems.

Animals↗

Temperature compensation in the escape response of a marine copepod, Calanus finmarchicus (Crustacea).

Calanus finmarchicus, the dominant mesozooplankter of the North Atlantic, is an important food source for many fishes and other planktivores. This species, which has limited diel vertical migration, depends on its fast-start escape response to evade predators. It has myelinated neuronal axons, which contribute to its rapid and powerful escape response. The thermal environment that C. finmarchicus inhabits ranges from below 0 degrees C to 16 degrees C. Previous studies have shown that respiration, growth, and reproductive rates are strongly dependent on temperature, with Q10 > 2.5. A comparable dependence of the escape response could place the animal at higher risk for cold-compensated predators. Our work focused on the temperature dependence of the behavioral response to stimuli that mimic predatory attacks. We found that in contrast to other biological processes, all aspects of the escape response showed a low dependence on temperature, with Q10 values below 2. This low temperature dependence was consistent for escape parameters that involved neural as well as muscle components of the behavioral response. These findings are discussed in the contexts of the predator-prey relations of copepods and the thermal dependence of behavior in other taxa.

Aging↗

Loss of escape-related giant neurons in a spiny lobster, Panulirus argus.

When attacked, many decapod crustaceans perform tailflips, which are triggered by a neural circuit that includes lateral giant interneurons, medial giant interneurons, and fast flexor motor giant neurons (MoGs). Slipper lobsters (Scyllaridae) lack these giant neurons, and it has been hypothesized that behavioral (e.g., digging) and morphological (e.g., flattening and armor) specializations in this group caused the loss of escape-related giant neurons. To test this hypothesis, we examined a species of spiny lobster, Panulirus argus. Spiny lobsters belong to the sister taxon of the scyllarids, but they have a more crayfish-like morphology than scyllarids and were predicted to have escape-related giant neurons. Ventral nerve cords of P. argus were examined using paraffin-embedded sections and cobalt backfills. We found no escape-related giant neurons and no large axon profiles in the dorsal region of the nerve cord of P. argus. Cobalt backfills showed one fewer fast flexor motor neuron than in species with MoGs and none of the fast flexor motor neurons show any of the anatomical specializations of MoGs. This suggests that all palinuran species lack this giant escape circuit, and that the loss of rapid escape behavior preceded, and may have driven, alternative predator avoidance and anti-predator strategies in palinurans.

Animals↗

[The effects of fear on individual and group escape in a computer simulated maze].

UNLABELLED: The purpose is to compare the effects of fear on escape behavior of individual and group conditions, in a computer-simulated maze. CRT display did not provide a bird's eye view of the maze, to the subjects, but only cues, what they would see, if they were actually inside of the maze. In the group escape condition, bodies and behaviors of other people were also shown in the maze. Subjects often got too close each other and collided with each other. THE RESULTS: Fear increased the time and locomotion required to reach the exit, because of the occurrence of a "traffic jam" in the group escape condition, however, fear reduced time in the individual escape condition. In addition, fear influenced types of escape behavior, depending on the form of maze.

Adult↗

Changes in the effects of d-amphetamine on escape responding by its prior effects on punished responding.

Responses of squirrel monkeys adjusted the intensity of a continuous electric shock under two different schedules. In one schedule, responses decreased a shock intensity which otherwise was increased at a fixed rate (escape). In the other schedule, responses produced food pellets but also increased a shock intensity which otherwise decreased at a fixed rate (punishment). When animals were first studied under the escape schedule, d-amphetamine increased responding. Similarly, when animals had an intervening experience under the punishment schedule with no drugs administered, or when the drug was given but shock increments were tempoerarily eliminated during those drug sessions, d-amphetamine still increased subsequent escape responding. However, when animals under the punishment schedule were given d-amphetamine and shock increments occurred as usual during the drug session, the drug no longer increased either punished or subsequent escape responding. The effects of d-amphetamine on escape responding were completely different depending on the individual's prior drug experience.

Animals↗

Central cellular mechanisms underlying temperature-dependent changes in the goldfish startle-escape behavior.

Activation of auditory afferents on the lateral dendrite of the Mauthner (M)-cell triggers an escape response (C-start) in goldfish. To study distinct behavioral changes and their physiological correlates on a cellular level we examined the effect of acute changes of temperature on M-cell membrane properties and intracellular responses to sound clicks and on C-start kinematics and behavior, focusing on threshold and initial escape direction, two properties determined on the M-cell level. Cooling slowed C-start motor performance, increasing response latency and decreasing peak velocity and peak acceleration, but increased the probability of triggering the escape. In addition, the likelihood of escapes in an inappropriate direction (e.g., responses toward the stimulus instead of away from it) increased at low temperatures. On a cellular level, cooling caused a distinct increase in input resistance of the M-cell and in the dendritic space constant for the auditory-evoked synaptic potentials. Moreover, cooling decreased the magnitude and delayed the onset of feedforward inhibition of the M-cell. These temperature-induced changes in the network and in the intrinsic M-cell properties combine to support behavioral hyperexcitability, but apparently also alter the directional decision-making process during an escape. More generally, our results illustrate that the balance between excitatory and inhibitory influences can determine the expression of a behavior and its modification and at the same time underline the significance of temperature for nervous system function and behavior.

Acoustic Stimulation↗

[THe selective effect of neuroleptics on a dopamine-dependent behavioral disorder in rats in the extrapolation escape test].

The low doses of neuroleptics restored the ability of 1-DOPA treated rats to escape behaviour from acute stress situation (in the extrapolation escape test). Non-antipsychotic benzamides and phenothiazine, antidepressants and benzodiazepine tranquilizers were inactive. On the whole, the effectiveness of neuroleptics was in accordance with clinical data. The loss of ability to escape in 1-DOPA treated rats was accompanied by stereotypes hyperlocomotion in the water. Various psychotropic drugs decreased only hyperactivity without the influence on escape behaviour. Both forms of behavioral pathology were prevented by central aromatic acid decarboxylase inhibitor. However, the loss of ability to escape behavior only is selective and sensitive to neuroleptics action.

Animals↗

Drug effects on attack defense and escape in mice.

The relative specificity and potency of action of 32 neuropsychotropic drugs was assessed on attacks, defensive upright postures and escapes occurring in singly-housed male mice during interactions with non-aggressive strange males. Scopolamine was most potent in reducing attacks while apomorphine was most active in stimulating attacks. Defenses and escapes were inhibited most efficiently by pentobarbital and diazepam, while L-tryptophan was most active of the tested drugs in stimulating defenses and escapes. Aminooxyacetic acid and valproate inhibited both attack and defensive-escape behavior at relatively low doses. Inhibition of attacks by many drugs tested could be explained by anticholinergic, serotonergic or gabaergic effects while stimulation of attacks may be due to dopaminergic effects. Gabaergic drug actions seem to inhibit while serotonergic effects might stimulate defenses and escapes.

Aggression↗

Altered excitability of the crayfish lateral giant escape reflex during agonistic encounters.

The excitability of the lateral giant escape reflex of socially dominant and submissive crayfish at rest and during agonistic encounters was studied and compared. During agonistic encounters the excitability of the lateral giant reflex falls, substantially in subordinates and slightly in dominants, whereas at rest excitability seems to be independent of social status. Thus, paradoxically, socially dominant animals are more likely to execute lateral giant escape reactions during interactions than are subordinates. It is suggested that subordinates under threat of attack tend to engage circuitry involved in flexible, nonreflex ("voluntary") types of escape not mediated by giant neurons and therefore inhibit giant neuron-mediated reflex circuitry that produces prompt, but less adaptive, responses. In contrast, dominants go about their business, mainly ignoring their conspecifics and relying on reflex escape to protect them from unexpected attack. Consistent with this view, escape of subordinates during agonistic encounters is mediated by nongiant, not reflex, circuitry. These observations and their interpretation suggest a possible functional role for recently described social status-dependent serotonergic modulation of the lateral giant reflex, which is inhibitory in sign in subordinates and facilitatory in dominants.

Agonistic Behavior↗

[The analysis of schizophrenic inpatients' escape behavior].

To study the escaping behavior of 1030 schizophrenic in-patients, "Brief Rating Scale for Dangerous Behavior of In-patient" was used to asses them within their first week hospitalization from May 1994 to March 1996. The result showed that 276 (26.8%) patients had escaping behavior. The patients with paranoid schizophrenia had higher rate of escaping behavior. There was no correlation being found between sex, age, duration of illness, and escaping behavior. The patients with the history of such behavior were more likely to escape from ward (41.9%). The suggestion for preventing such behavior were discussed.

Adolescent↗

Mechanisms of escape from CD8+ T-cell clones specific for the HER-2/neu proto-oncogene expressed in ovarian carcinomas: related and unrelated to decreased MHC class 1 expression.

We have developed an in vitro model to study mechanisms by which ovarian tumor cells that over-express the HER-2/neu proto-oncogene escape recognition by TCD8+. Nine tumor-specific, HLA A2-restricted TCD8+ clones were isolated from 2 ovarian tumor-specific TCD8+ lines derived from tumor-infiltrating or -associated lymphocytes. Of these, 2 clones recognized the previously defined HER-2/neu epitope E75 (a.a. 369-377) and one recognized the C85 epitope (a.a. 971-979), whereas the specificity of the remaining 6 clones was unknown. Three different tumor escape variants (EVC8, EVC22 and EVC36) were produced by co-culturing an ovarian tumor line over-expressing HER-2/neu with these autologous TCD8+ clones. Cell surface expression of HLA A2 was markedly decreased on all 3 escape variants, relative to the parental tumor line, while no significant decrease in their expression of the HER-2/neu, ICAM-1 or LFA-3 molecules was found. There was a correlation between the level of tumor-specific recognition and HLA A2 expression among the tumor clones isolated from 2 of the escape variants (EVC8 and EVC36). In contrast, high HLA A2-expressing tumor clones isolated from the EVC22 variant, or EVC22 which had regained high HLA A2 expression through IFN-gamma treatment, were not recognized by the HER-2/neu-specific TCD8+ clone C-22. No mutations were found in the cDNA or the genomic DNA derived from the PCR product corresponding to a 496 bp fragment including the region coding for the E75 epitope of the HER2/neu gene in the EVC22 variant. Collectively, this in vitro model underlines the importance of decreased expression of the HLA restriction element for escape from tumor-specific TCD8+ but also demonstrates that additional mechanisms exist.

Down-Regulation↗

Spatial reference memory in GluR-A-deficient mice using a novel hippocampal-dependent paddling pool escape task.

Genetically modified mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit, GluR-A (GluR1), and deficient in hippocampal CA3-CA1 long-term potentiation (LTP), were assessed on a novel, hippocampal-dependent spatial reference memory, paddling pool escape task. The mice were required to use the extramaze cues around the laboratory to find a hidden escape tube that was in a constant location at one of 12 possible positions around the perimeter of the paddling pool, in order to escape from shallow water. The knockout mice performed well on this task. They displayed a small initial impairment (in terms of both escape latencies and choice errors), but they were soon as efficient as the wild-type mice in escaping from the water. This was further demonstrated by performance during a 20-s probe trial in which the exit tube was blocked. Both groups of mice spent most of the time searching in the quadrant of the pool in which the exit tube had previously been located. In a subsequent experiment, entirely normal spatial acquisition was observed in the knockout mice when the paddling pool was moved to a novel spatial environment. The GluR-A -/- mice were also unimpaired in a further reversal phase in which the correct exit location was moved by 180 degrees around the perimeter wall. These results are consistent with previous watermaze studies, providing further demonstration of intact hippocampus-dependent spatial reference memory in GluR-A knockout mice. They contrast strikingly with the profound deficits in hippocampus-dependent, short-term, flexible spatial working memory observed in these knockout mice. This study also demonstrates a novel behavioral task for assessing spatial memory in genetically modified mice. This task shares the behavioral profile of the well-established watermaze paradigm, but may have advantages for the study of genetically modified mice.

Animals↗

HTLV-I viral escape and host genetic changes in the development of adult T cell leukemia.

In the pathogenesis of adult T cell leukemia (ATL), an oncogenetic role of the human T cell lymphotropic virus type I (HTLV-I) Tax protein, viral escape from the host immune system, and host genetic changes have been proposed as contributory factors. We examined the premature stop codons in tax gene as one of the mutations that may lead to escape of HTLV-I from the cytotoxic T lymphocyte (CTL) response in HTLV-I carriers, to test whether a putative CTL escape mutant can emerge in the early stage of ATL development and whether HTLV-I infected cells with such a mutation can proliferate subsequently. We also examined deletion of cyclin-dependent kinase inhibitor 4 (INK4) genes and mutation of p53 gene in combination with changes in the HTLV-I genome in acute type ATL to test whether host genetic changes promoted the malignant transformation of ATL cells that carry putative CTL escape mutations. The premature stop codon in tax gene existed in many non-ATL HTLV-I carriers as a minor population but not in the commonest HTLV-I sequence of the individual. This minor population with a premature stop codon did not expand subsequently in 3 asymptomatic carriers tested. There were cases who had a mutation or deletion in HTLV-I who also have either deletion of INK4 genes or mutation in p53 gene. Our findings suggest that CTL escape mutation can occur at an early stage of ATL development, and that certain host genetic changes favor the development of the aggressive form of ATL.

Cell Proliferation↗

The mechanism of escape of plasma protein from small blood vessels in the mucosa of the small intestine of the rat.

A study has been made in rats of the relative rates of escape of plasma protein, measured by accumulation of Evans Blue, and of the large marker particle, HgS, into uninjured small bowel and into an area of intradermal injection of histamine. The rate of escape of Evans Blue, per unit mass of tissue, into small bowel and into an area of histamine-stimulated skin were found to be almost the same, but leakage of HgS into the bowel was only about 1/10 of leakage of the same tracer into a site of intradermal histamine injection. If it be assumed, as is generally accepted, that all the protein that leaks from histamine-stimulated vessels does so via gaps in vascular endothelium that are large enough to allow escape of large marker particles like HgS, these findings show that only a small fraction of the protein that leaks into normal intestinal mucosa can escape via gaps, and that most of the leakage must occur by a route not permeable to particles of HgS. The findings give no indication of the nature of the alternative route for escape of protein.

Animals↗

The HIV-1 V3 domain on field isolates: participation in generation of escape virus in vivo and accessibility to neutralizing antibodies.

The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3 peptides corresponding to field isolates were highly immunogenic but failed to induce neutralizing or gp120-precipitating Abs. On the contrary, V3 peptide corresponding to the laboratory strain HXB2 induced HIV neutralizing, gp120-precipitating immune serum. In conclusion, these data suggest a participation of the V3 domain in the immunoselection of escape virus, and that V3 on early field virus is less accessible to NA than that on laboratory strains.

Amino Acid Sequence↗