PubMed Health⌕ Search

Biomedical subjects

Robert Gerlai

Publications and source records attributed to Robert Gerlai.

13 recordsLinked to original sources
PubMed2006

Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish (Danio rerio).

The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.g., rodents, zebrafish behavior is understudied and very few behavioral paradigms exist for mutation or drug screening purposes. Alcoholism is one of the biggest and costliest diseases whose mechanisms are not well understood. Model organisms such as the zebrafish may be utilized in this line of research. Previously, we investigated the effects of acute ethanol exposure on adult zebrafish using four behavioral paradigms and employing manual quantification methods. Here, we study the effects of chronic ethanol exposure and analyze how it modifies the effects of acute ethanol treatment. We employ a videotracking-based automated quantification method in a predator model paradigm and show that this method is capable of detecting an avoidance reaction that is ameliorated by higher doses of ethanol, a potential anxiolytic effect. Importantly, we also demonstrate that chronic, two week long, exposure to ethanol results in significant adaptation to this substance in adult zebrafish. Overall, our results suggest that zebrafish will be an appropriate subject for high throughput screening applications aimed at the analysis of the mechanisms and pharmacology of acute and chronic ethanol induced changes in the vertebrate brain.

Alcoholism↗
PubMed2006

Fishing for genes influencing vertebrate behavior: zebrafish making headway.

The zebrafish (Danio rerio) has been a favorite model of developmental biologists and geneticists, but only recently have investigators begun to appreciate its usefulness in behavior genetics. Papers focusing on the behavior or brain function of this species were once extremely rare, but during the past decade rapid growth has taken place. Despite the increased interest, however, the number of studies devoted to the analysis of the behavior of this species is still orders of magnitude less than those conducted on more traditional laboratory subjects including the rat and the mouse. The authors review selected literature and demonstrate that zebrafish is an excellent subject for behavior genetics research, especially in the area of forward genetics (mutagenesis).

Animals↗
PubMed2006

Behavioral phenotyping in zebrafish: comparison of three behavioral quantification methods.

The zebrafish has been popular in developmental biology and genetics, but its brain function has rarely been studied. High-throughput screening of mutation or drug-induced changes in brain function requires simple and automatable behavioral tests. This article compares three behavioral quantification methods in four simple behavioral paradigms that test a range of characteristics of adult zebrafish, including novelty-induced responses, social behavior, aggression, and predator-model-induced responses. Two quantification methods, manual recording and computerized videotracking of location and activity, yielded very similar results, suggesting that automated videotracking reliably measures activity parameters and will allow high-throughput screening. However, observation-based event recording of posture patterns was found generally not to correlate with videotracking measures, suggesting that further refinement of automated behavior quantification may be considered.

Aggression↗
PubMed2004

Autism: a target of pharmacotherapies?

Autism is reaching epidemic proportions. The diagnosis can be made as early as 2 years of age, and autistic patients are expected to have a normal life span. Thus, in terms of the number of 'patient years', autism spectrum disorder (ASD) represents a market that is as large as that of the biggest neurological indication, Alzheimer's disease. However, despite the clear unmet medical need no effective treatment is yet available. This could be because the biology of ASD is not clearly understood and thus proper drug treatment has not been possible. However, significant advances are being made toward understanding the mechanisms of the disease. Here, we review the most recent preclinical advances in the hope that they will lead to a breakthrough in the near future.

Animals↗
PubMed2003

Autism: a large unmet medical need and a complex research problem.

Autism has been becoming the focus of attention as its apparently increasing prevalence is better appreciated. According to some estimates, the frequency of children with autistic spectrum disorder (ASD) can be as high as 1 in 150. The diagnosis can be made as early as 2 years of age, and autistic patients often have a normal life span. Thus, in terms of the number of "patient years," ASD represents a market that is as large as that of the biggest neurological indication, Alzheimer's disease. Despite the clear unmet medical need, no effective treatment is available. This may be because the mechanism of ASD is not understood. The aim of the present paper is to review recent advances in autism research and to discuss some of the most stressing problems mainly from a preclinical research standpoint. We hope to draw attention to the need to study this devastating disease that places an enormous burden on the society in general and the relatives and caregivers of autistic patients in particular.

Animals↗
PubMed2003

Zebra fish: an uncharted behavior genetic model.

The zebra fish has been a preferred subject of genetic analysis. It produces a large number of offspring that can be kept in small aquaria, it can be easily mutagenized using chemical mutagens (e.g., ethyl nitrosourea [ENU]), and high-resolution genetic maps exist that aid identification of novel genes. Libraries containing large numbers of mutant fish have been generated, and the genetic mechanisms of the development of zebra fish, whose embryo is transparent, have been extensively studied. Given the extensive homology of its genome with that of other vertebrate species including our own and given the available genetic tools, zebra fish has become a popular model organism. Despite this popularity, however, surprisingly little is known about its behavior. It is argued that behavioral analysis is a powerful tool with which the function of the brain may be studied, and the zebra fish will represent an excellent subject of such analysis. The present paper is a proof of concept study that uses pharmacological manipulation (exposure to alcohol) to show that the zebra fish is amenable to the behavioral genetic analysis of aggression and thus may allow us to reveal molecular mechanisms of this behavioral phenomenon relevant to vertebrates.

Aggression↗
PubMed2002

Behavioral impairment of APP(V717F) mice in fear conditioning: is it only cognition?

Alzheimer's Disease (AD) is a devastating human neurodegenerative disorder associated with progressive deterioration of cognitive abilities. The APP(V717F) mouse, an animal model of AD showing robust overexpression of the human amyloid precursor protein (APP) carrying the mutation 717 V --> F, was also shown to exhibit learning and memory performance deficits. However, AD patients suffer from other abnormalities including altered emotionality. Emotionality has not been analyzed in AD mouse models. Here, motor and posture patterns exhibited by APP(V717F) mice are described in a detailed manner in fear conditioning, a paradigm that allows one to test both mnemonic and emotional characteristics of mice. Our results revealed a complex set of behavioral alterations in APP(V717F) mice in measures of exploratory behavior and fear suggesting that the effects of APP(V717F) overexpression in this mouse model are not limited to cognition and may need to be thoroughly examined in the future in a broad range of behavioral tests.

Alzheimer Disease↗
PubMed2002

Altered performance characteristics in cognitive tasks: comparison of the albino ICR and CD1 mouse strains.

With the advent of recombinant DNA technology the mouse has become a favored model organism in brain research. Numerous mouse strains are available to use as a host for carrying genetic alteration induced by targeted or random mutagenesis. Most strains differ in their genetic makeup and phenotypical characteristics. The choice of the host strain thus can be crucial for the analysis of functional effects of the induced mutation. In the present paper we analyze the behavior of two related outbred albino strains of mice, ICR and CD1, that are often used in transgenic research. Using two frequently employed learning tasks, the Morris water maze (MWM) and the context-dependent fear conditioning (CFC) as well as other behavioral tests, we demonstrate significant performance differences between the strains. ICR suffers from a severe visual impairment making this strain difficult to use in several behavioral paradigms that require good visual perception, e.g. the MWM. CD1 does not suffer from grossly impaired vision but, similarly to the ICR strain, CD1 mice exhibit decreased freezing in all phases of CFC. Although the strains are able to learn, such deficits can render them significantly impaired dependent on the performance demands of the cognitive test employed. Our findings underscore the need for careful examination of the characteristics of the host strain, the choice of which must be made in accordance with the expected functional alterations induced by the mutation.

Animals↗
PubMed2002

Force transducer-based movement detection in fear conditioning in mice: a comparative analysis.

Fear conditioning (FC) allows the dissociation of hippocampal and nonhippocampal behavioral function in rodents, and has become a diagnostic tool in transgenic mouse research employed to investigate mutation-induced changes in brain function. Although the procedural details of the paradigm have been established, quantification of the behavioral output, freezing, remains problematic in mice. Observation-based techniques are time-consuming and may be subject to bias, while movement detection with photocells is imprecise. Here we describe an alternative method for movement detection, based on an electronic force transducer system that allows the quantification of acceleration forces generated by a moving subject. We compare the behavior of two inbred strains of mice (C57BL/6 and DBA/2) whose performance is known to differ in hippocampal tasks, including FC. The comparison is made using multiple techniques: the force transducer approach, and three observation-based methods, a computer-aided event-recording approach, a traditional time-sampling paper/pencil method, and a subjective impression-based scoring system. In addition, we investigate the correlation structures of behavioral elements quantified by event recording, using principal component analyses; we conclude that fear may manifest in multiple forms and in a stimulus- and genotype-dependent manner. We suggest that the force transducer system provides precise quantification of movements in an automated manner and will allow high-throughput screening for mutation and drug effects in mice. However, we also argue that fear responses can be complex, and freezing behavior may not be the only measure of fear or fear-associated memory.

Animals↗
PubMed2002

Hippocampal LTP and memory in mouse strains: is there evidence for a causal relationship?

The mechanisms underlying memory are under intense investigation. One of the most promising candidates at the cellular level is long-term potentiation (LTP). Numerous pharmacological and molecular genetic manipulations have led to alteration in both LTP and memory. However, the causal relationship between these phenotypical changes is debated. The problem of causality can be addressed in numerous ways. One suggestion is to investigate natural variation in both LTP and memory performance in mouse strains. If variation in synaptic and behavioral phenomena is found, correlation between these traits may be investigated. The advantages and disadvantages of this approach are discussed. An empirical example using four mouse strains is also presented to highlight some general problems. The following arguments are made. First, multiple electrophysiological and behavioral paradigms with idiosyncratic condition characteristics should be conducted to avoid false-positive findings due to alterations unrelated to memory and its mechanisms. Multiple stimulation and memory protocols may also allow one to study the complexity and multiplicity of processes. Second, analysis of a large number of mouse strains may be needed to avoid false interpretation of results due to spurious gene associations and/or linkage disequilibrium. Third, quantitative genetic analysis using, for example, diallele crosses, may be employed to properly investigate biologically meaningful, i.e., genetic, effects. It is concluded that with the use of additional methods (e.g., QTL analysis, gene expression arrays, and biochemical analysis) providing converging evidence, analysis of mouse strains will be instrumental in addressing the question regarding the role LTP may play in memory.

Animals↗
PubMed2002

Phenomics: fiction or the future?

The ease with which genetic mutations can be induced in or introduced into mammalian organisms, such as the mouse, has created a significant need for phenotypic analysis. Developments in computer technology, instrumentation and bioinformatics, as well as in numerous neuroscience disciplines, will help to meet the demands set by the molecular revolution. As a result, the field of 'phenomics' is being born. This will integrate multidisciplinary research, with the goal of understanding the complex phenotypic consequences of genetic mutations at the level of the organism. This paper focuses on one of the disciplines that show promising developments, behavioral science.

Animals↗