Blocking the ErbB pathway during adolescence affects the induction of anxiety-like behavior in young adult maternal immune activation offspring.

Epidemiological and experimental evidence demonstrates that maternal exposure to infection during gestation increases the offspring's risk of developing schizophrenia and other neurodevelopmental disorders. In addition, the NRG-ErbB4 signaling pathway is involved in brain development and neuropsychiatric disorders. Specifically, this pathway modulates the dopaminergic and GABAergic systems and is expressed in the early stages of prenatal development.

Long-term effects of prophylactic MgSO in maternal immune activation rodent model at adolescence and adulthood.

The effects of MgSO as an anti-inflammatory agent in pregnant women have been investigated in the last few years. Infections can cause an inflammatory reaction involving the placenta membranes and amniotic cavity. They may have short-term effects on the mother and her fetuses, like preterm birth, cerebral palsy, and developmental delay.

Exploration in the Presence of Mother in Typically and Non-typically Developing Pre-walking Human Infants.

In previous phenotyping studies of mouse and rat exploratory behavior we developed a computational exploratory data analysis methodology including videotaping, tracking, preparatory methods for customized data analysis, a methodology for improving the replicability of results across laboratories, and algorithmic design for exposing the natural reference places (origins) used by animals during exploration. We then measured the animals' paths in reference to these origins, revealing robust, highly replicable modules termed excursions, which are performed from the origin into the environment and back to the origin. Origin-related exploration has been claimed to be phylogenetically conserved across the vertebrates.

Health benefits of a physical exercise program for inpatients with mental health; a pilot study.

The positive effect of exercise on human health and the relationship between physical activity, health, and wellbeing are well studied and extensively documented in the literature. However, considerably less attention is devoted to the impact of exercise on mental health and wellbeing for people experiencing a mental illness, in general, and in particular for inpatients in the mental health care system. Here, we determine the clinical feasibility and effects of short-term (up to three months) vs long-term (up to six months) group-based exercise program for inpatients with chronic mental health.

The influence of immune activation at early vs late gestation on fetal NRG1-ErbB4 expression and behavior in juvenile and adult mice offspring.

Maternal inflammation during pregnancy is associated with a higher incidence of mental disorders (e.g. schizophrenia and autism) in the offspring.

Vertical exploration and dimensional modularity in mice.

Exploration is a central component of animal behaviour studied extensively in rodents. Previous tests of free exploration limited vertical movement to rearing and jumping. Here, we attach a wire mesh to the arena wall, allowing vertical exploration.

Reproducibility and replicability of rodent phenotyping in preclinical studies.

The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues.

ErbB signaling antagonist ameliorates behavioral deficit induced by phencyclidine (PCP) in mice, without affecting metabolic syndrome markers.

Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed.

Decoding emotion of the other differs among schizophrenia patients and schizoaffective patients: A pilot study.

The deficit in ability to attribute mental states such as thoughts, beliefs, and intentions of another person is a key component in the functional impairment of social cognition in schizophrenia. In the current study, we compared the ability of persons with first episode schizophrenia (FE-SZ) and individuals with schizophrenia displaying symptomatic remission (SZ-CR) to decode the mental state of others with healthy individuals and schizoaffective patients. In addition, we analyzed the effect of dopamine-related genes polymorphism on the ability to decode the mental state of another, and searched for different genetic signatures.

Behavioral characterization of blocking the ErbB signaling during adolescent and adulthood in reward-liking (preference) and reward-related learning.

Adolescence is a critical period in brain development. During this critical period the seeking for hedonic activities is increased, and their activity signals are stronger than the regulatory signals of judgment and reasoning. We recently reported that alteration of ErbB signaling during this period led to elevated striatal dopamine levels and reduced preference for sweetness without affecting locomotor activity and exploratory behavior.

Generative rules of Drosophila locomotor behavior as a candidate homology across phyla.

The discovery of shared behavioral processes across phyla is a significant step in the establishment of a comparative study of behavior. We use immobility as an origin and reference for the measurement of fly locomotor behavior; speed, walking direction and trunk orientation as the degrees of freedom shaping this behavior; and cocaine as the parameter inducing progressive transitions in and out of immobility. We characterize and quantify the generative rules that shape Drosophila locomotor behavior, bringing about a gradual buildup of kinematic degrees of freedom during the transition from immobility to normal behavior, and the opposite narrowing down into immobility.

Coping with Space Neophobia in Drosophila melanogaster: The Asymmetric Dynamics of Crossing a Doorway to the Untrodden.

We discover and examine within a wide phylogenetic perspective spatial neophobia, avoidance of untrodden terrain, in fruit flies, in an experimental setup that reduces the gap between the field and the laboratory. In our setup, fruit flies use a natal fruit as their origin, freely exploring for days their surroundings, which consists of a mixture of trodden and untrodden terrain. The interface between trodden and untrodden is, however, reduced in our setup to a wide doorway, opened within a surrounding wall.

Disruption of the ErbB signaling in adolescence increases striatal dopamine levels and affects learning and hedonic-like behavior in the adult mouse.

The ErbB signaling pathway has been genetically and functionally implicated in schizophrenia. Numerous findings support the dysregulation of Neuregulin (NRG) and epidermal growth factor (EGF) signaling in schizophrenia. However, it is unclear whether alterations of these pathways in the adult brain or during development are involved in the pathophysiology of schizophrenia.

Display of individuality in avoidance behavior and risk assessment of inbred mice.

Factors determining individuality are still poorly understood. Rodents are excellent model organisms to study individuality, due to a rich behavioral repertoire and the availability of well-characterized isogenic populations. However, most current behavioral assays for rodents have short test duration in novel test environments and require human interference, which introduce coercion, thereby limiting the assessment of naturally occurring individuality.

The angular interval between the direction of progression and body orientation in normal, alcohol- and cocaine treated fruit flies.

In this study we characterize the coordination between the direction a fruit-fly walks and the direction it faces, as well as offer a methodology for isolating and validating key variables with which we phenotype fly locomotor behavior. Our fundamental finding is that the angular interval between the direction a fly walks and the direction it faces is actively managed in intact animals and modulated in a patterned way with drugs. This interval is small in intact flies, larger with alcohol and much larger with cocaine.

Measuring behavior of animal models: faults and remedies.

Widely used behavioral assays need re-evaluation and validation against their intended use. We focus here on measures of chronic anxiety in mouse models and posit that widely used assays such as the open-field test are performed at the wrong time, for inadequate durations and using inappropriate mouse strains. We propose that behavioral assays be screened for usefulness on the basis of their replicability across laboratories.

Short and long term measures of anxiety exhibit opposite results.

Animal models of human diseases of the central nervous system, generalized anxiety disorder included, are essential for the study of the brain-behavior interface and obligatory for drug development; yet, these models fail to yield new insights and efficacious drugs. By increasing testing duration hundredfold and arena size tenfold, and comparing the behavior of the common animal model to that of wild mice, we raise concerns that chronic anxiety might have been measured at the wrong time, for the wrong duration, and in the wrong animal. Furthermore, the mice start the experimental session with a short period of transient adaptation to the novel environment (habituation period) and a long period reflecting the respective trait of the mice.

The developmental dynamics of behavioral growth processes in rodent egocentric and allocentric space.

In this review I focus on how three methodological principles advocated by Philip Teitelbaum influenced my work to this day: that similar principles of organization should be looked for in ontogeny and recovery of function; that the order of emergence of behavioral components provides a view on the organization of that behavior; and that the components of behavior should be exhibited by the animal itself in relatively pure form. I start by showing how these principles influenced our common work on the developmental dynamics of rodent egocentric space, and then proceed to describe how these principles affected my work with Yoav Benjamini and others on the developmental dynamics of rodent allocentric space. We analyze issues traditionally addressed by physiological psychologists with methods borrowed from ethology, EW (Eshkol-Wachman) movement notation, dynamical systems and exploratory data analysis.

Validation of the dimensionality emergence assay for the measurement of innate anxiety in laboratory mice.

The open field test is a common tool to measure innate anxiety in rodents. In the usual configuration of this test the animal is forced to explore the open arena and its behavior includes both anxiety and non-anxiety responses. However, the open arena is generally small and allows only limited expression of exploratory behavior.

Quantifying the buildup in extent and complexity of free exploration in mice.

To obtain a perspective on an animal's own functional world, we study its behavior in situations that allow the animal to regulate the growth rate of its behavior and provide us with the opportunity to quantify its moment-by-moment developmental dynamics. Thus, we are able to show that mouse exploratory behavior consists of sequences of repeated motion: iterative processes that increase in extent and complexity, whose presumed function is a systematic active management of input acquired during the exploration of a novel environment. We use this study to demonstrate our approach to quantifying behavior: targeting aspects of behavior that are shown to be actively managed by the animal, and using measures that are discriminative across strains and treatments and replicable across laboratories.

Ten ways to improve the quality of descriptions of whole-animal movement.

The demand for replicability of behavioral results across laboratories is viewed as a burden in behavior genetics. We demonstrate how it can become an asset offering a quantitative criterion that guides the design of better ways to describe behavior. Passing the high benchmark dictated by the replicability demand requires less stressful and less restraining experimental setups, less noisy data, individually customized cutoff points between the building blocks of movement, and less variable yet discriminative dynamic representations that would capture more faithfully the nature of the behavior, unmasking similarities and differences and revealing novel animal-centered measures.

Knots: attractive places with high path tortuosity in mouse open field exploration.

When introduced into a novel environment, mammals establish in it a preferred place marked by the highest number of visits and highest cumulative time spent in it. Examination of exploratory behavior in reference to this "home base" highlights important features of its organization. It might therefore be fruitful to search for other types of marked places in mouse exploratory behavior and examine their influence on overall behavior.

Freedom of movement and the stability of its unfolding in free exploration of mice.

Exploration is a central component of human and animal behavior that has been studied in rodents for almost a century. The measures used by neuroscientists to characterize full-blown exploration are limited in exposing the dynamics of the exploratory process, leaving the morphogenesis of its structure and meaning hidden. By unfettering exploration from constraints imposed by hunger, thirst, coercion, and the confines of small cage and short session, using advanced computational tools, we reveal its meaning in the operational world of the mouse.