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Ralph J Greenspan

Publications and source records attributed to Ralph J Greenspan.

At least 19 recordsLinked to original sources
PubMed2006

Molecular analysis of flies selected for aggressive behavior.

Aggressive behavior is pervasive throughout the animal kingdom, and yet very little is known about its molecular underpinnings. To address this problem, we have developed a population-based selection procedure to increase aggression in Drosophila melanogaster. We measured changes in aggressive behavior in the selected subpopulations with a new two-male arena assay. In only ten generations of selection, the aggressive lines became markedly more aggressive than the neutral lines. After 21 generations, the fighting index increased more than 30-fold. Using microarray analysis, we identified genes with differing expression levels in the aggressive and neutral lines as candidates for this strong behavioral selection response. We tested a small set of these genes through mutant analysis and found that one significantly increased fighting frequency. These results suggest that selection for increases in aggression can be used to molecularly dissect this behavior.

Aggression↗
PubMed2006

The nature of genetic influences on behavior: lessons from "simpler" organisms.

Substantial advances have been made in recent years in the understanding of the genetic basis of behavior in "simpler" organisms, especially the mouse and the fruit fly Drosophila. The authors examine the degree of similarity between the genetic underpinnings of psychiatric illness and genetic influences on behavior in such simpler organisms. Six topics are reviewed: 1) the extent of natural genetic variation, 2) the multigenic nature of natural variation, 3) the impact of individual genes on multiple traits, 4) gene-environment interactions, 5) genetic effects on the environment, and 6) gene-by-sex interactions. The results suggest that the pattern of results emerging in psychiatric genetics is generally consistent with the findings of behavioral genetics in simpler organisms. Across the animal kingdom, individual differences in behavior are nearly always influenced by genetic factors which, in turn, result from a substantial number of individual genes, each with a small effect. Nearly all genes that affect behavior influence multiple phenotypes. The impact of individual genes can be substantially modified by other genes and/or by environmental experiences. Many animals alter their environment, and the nature of that alteration is influenced by genes. For some behaviors, the pathway from genes to behavior differs meaningfully in males and females. With respect to the broad patterns of genetic influences on behavior, Homo sapiens appears to be typical of other animal species.

Animals↗
PubMed2005

Dopaminergic modulation of arousal in Drosophila.

BACKGROUND: Arousal levels in the brain set thresholds for behavior, from simple to complex. The mechanistic underpinnings of the various phenomena comprising arousal, however, are still poorly understood. Drosophila behaviors have been studied that span different levels of arousal, from sleep to visual perception to psychostimulant responses. RESULTS: We have investigated neurobiological mechanisms of arousal in the Drosophila brain by a combined behavioral, genetic, pharmacological, and electrophysiological approach. Administration of methamphetamine (METH) suppresses sleep and promotes active wakefulness, whereas an inhibitor of dopamine synthesis promotes sleep. METH affects courtship behavior by increasing sexual arousal while decreasing successful sexual performance. Electrophysiological recordings from the medial protocerebrum of wild-type flies showed that METH ingestion has rapid and detrimental effects on a brain response associated with perception of visual stimuli. Recordings in genetically manipulated animals show that dopaminergic transmission is required for these responses and that visual-processing deficits caused by attenuated dopaminergic transmission can be rescued by METH. CONCLUSIONS: We show that changes in dopamine levels differentially affect arousal for behaviors of varying complexity. Complex behaviors, such as visual perception, degenerate when dopamine levels are either too high or too low, in accordance with the inverted-U hypothesis of dopamine action in the mammalian brain. Simpler behaviors, such as sleep and locomotion, show graded responses that follow changes in dopamine level.

Animals↗
PubMed2005

Flexibility in a gene network affecting a simple behavior in Drosophila melanogaster.

Gene interactions are emerging as central to understanding the realization of any phenotype. To probe the flexibility of interactions in a defined gene network, we isolated a set of 16 interacting genes in Drosophila, on the basis of their alteration of a quantitative behavioral phenotype-the loss of coordination in a temperature-sensitive allele of Syntaxin1A. The interactions inter se of this set of genes were then assayed in the presence and in the absence of the original Syntaxin1A mutation to ask whether the relationships among the 16 genes remain stable or differ after a change in genetic context. The pattern of epistatic interactions that occurs within this set of variants is dramatically altered in the two different genetic contexts. The results imply considerable flexibility in the network interactions of genes.

Alleles↗
PubMed2005

Consciousness eclipsed: Jacques Loeb, Ivan P. Pavlov, and the rise of reductionistic biology after 1900.

The life sciences in the 20th century were guided to a large extent by a reductionist program seeking to explain biological phenomena in terms of physics and chemistry. Two scientists who figured prominently in the establishment and dissemination of this program were Jacques Loeb in biology and Ivan P. Pavlov in psychological behaviorism. While neither succeeded in accounting for higher mental functions in physical-chemical terms, both adopted positions that reduced the problem of consciousness to the level of reflexes and associations. The intellectual origins of this view and the impediment to the study of consciousness as an object of inquiry in its own right that it may have imposed on peers, students, and those who followed is explored.

Behaviorism↗
PubMed2004

'Am not I a fly like thee?' From genes in fruit flies to behavior in humans.

The fruit fly Drosophila melanogaster has provided insight into the role of genes in behavior, some of which have relevant implications for humans. Mutants induced or engineered in the laboratory have contributed to our understanding of biological rhythms, learning, memory, neurodegenerative disease and drug response. Studies of naturally occurring genetic variation in behavior have advanced our understanding of what kinds of variants arise spontaneously and contribute to behavior.

Animals↗
PubMed2004

Excitatory and inhibitory switches for courtship in the brain of Drosophila melanogaster.

BACKGROUND: Courtship is the best-studied behavior in Drosophila melanogaster, and work on its anatomical basis has concentrated mainly on the functional identification of sexually dimorphic sites in the brain. Much less is known of the more expansive, nondimorphic, but nonetheless essential, neural elements subserving male courtship behavior. RESULTS: Sites in the CNS mediating initiation and early steps of male courtship in Drosophila melanogaster were identified by analyzing the behavior of mosaic flies expressing transgenes designed either to suppress neurotransmission or enhance neuronal excitability. Suppression of neurotransmission was accomplished by means of the dominantly acting, temperature-sensitive dynamin mutation shibire(ts1), whereas enhanced neuronal excitability was produced by means of a novel, dominantly acting, truncated eag potassium channel. By using a new, landmark-based procedure for aligning diverse expression patterns among the various mosaic strains, a comparison of courtship performance and affected brain sites in strains expressing the transgenes identified a cluster of cells in the posterior lateral protocerebrum that exerts reciprocal effects on the initiation of courtship, suppressing it when they are inactivated and enhancing it when they are hyperactivated, indicative of cells that normally play an excitatory, triggering role. A separate group of nearby cells, slightly more anterior in the lateral protocerebrum, was found to inhibit courtship when its activity is enhanced, indicative of an inhibitory role in courtship. CONCLUSIONS: A cluster of cells, some excitatory and some inhibitory, in the lateral protocerebrum regulates courtship initiation in Drosophila. These cells are likely to be an integration center for the multiple sensory inputs that trigger male courtship.

Analysis of Variance↗
PubMed2004

Cognitive consonance: complex brain functions in the fruit fly and its relatives.

The fruit fly, Drosophila melanogaster, has become a model for the study of a growing number of human characteristics because of the power of its genetics. Higher cognitive functions, however, might be assumed to be out of reach for the little fly. But the cumulative history of cognitive studies in insects and some of their arachnid relatives, as well as specific probing of the capabilities of fruit flies, suggests that even in this ethereal realm these creatures have much to contribute. What are the degrees of sophistication in cognitive behavior displayed by these organisms, how have they been demonstrated, and what is their potential for understanding how our own brains work?

Animals↗
PubMed2004

E pluribus unum, ex uno plura: quantitative and single-gene perspectives on the study of behavior.

Genetic studies of behavior have traditionally come in two flavors: quantitative genetic studies of natural variants and single-gene studies of induced mutants. Each employed different techniques and methods of analysis toward the common, ultimate goal of understanding how genes influence behavior. With the advent of new genomic technologies, and also the realization that mechanisms underlying behavior involve a considerable degree of complex gene interaction, the traditionally separate strands of behavior genetics are merging into a single, synthetic strategy.

Animals↗
PubMed2003

RNA and memory: from feeding to localization.

Ideas about the role of RNA in learning and memory have a checkered past. A new study in Drosophila, synthesizing classical forward genetics with DNA microarrays, brings us closer to seeing that role clearly.

Animals↗
PubMed2003

Salience modulates 20-30 Hz brain activity in Drosophila.

Fruit flies selectively orient toward the visual stimuli that are most salient in their environment. We recorded local field potentials (LFPs) from the brains of Drosophila melanogaster as they responded to the presentation of visual stimuli. Coupling of salience effects (odor, heat or novelty) to these stimuli modulated LFPs in the 20-30 Hz range by evoking a transient, selective increase. We demonstrated the association of these responses with behavioral tracking and initiated a genetic approach to investigating neural correlates of perception.

Action Potentials↗
PubMed2002

Electrophysiological correlates of rest and activity in Drosophila melanogaster.

Extended periods of rest in Drosophila melanogaster resemble mammalian sleep states in that they are characterized by heightened arousal thresholds and specific alterations in gene expression. Defined as inactivity periods spanning 5 or more min, amounts of this sleep-like state are, as in mammals, sensitive to prior amounts of waking activity, time of day, and pharmacological intervention. Clearly recognizable changes in the pattern and amount of brain electrical activity accompany changes in motor activity and arousal thresholds originally used to identify mammalian sleeping behavior. Electroencephalograms (EEGs) and/or local field potentials (LFPs) are now widely used to quantify sleep state amounts and define types of sleep. Thus, slow-wave sleep (SWS) is characterized by EEG spindles and large-amplitude delta-frequency (0-3.5 Hz) waves. Rapid-eye movement (REM) sleep is characterized by irregular gamma-frequency cortical EEG patterns and rhythmic theta-frequency (5-9 Hz) hippocampal EEG activity. It is unknown whether rest and activity in Drosophila are associated with distinct electrophysiological correlates. To address this issue, we monitored motor activity levels and recorded LFPs in the medial brain between the mushroom bodies, structures implicated in the modulation of locomotor activity, of Drosophila. The results indicate that LFPs can be reliably recorded from the brains of awake, moving fruit flies, that targeted genetic manipulations can be used to localize sources of LFP activity, and that brain electrical activity of Drosophila is reliably correlated with activity state.

Acclimatization↗
PubMed2002

Identification of genes involved in Drosophila melanogaster geotaxis, a complex behavioral trait.

Identifying the genes involved in polygenic traits has been difficult. In the 1950s and 1960s, laboratory selection experiments for extreme geotaxic behavior in fruit flies established for the first time that a complex behavioral trait has a genetic basis. But the specific genes responsible for the behavior have never been identified using this classical model. To identify the individual genes involved in geotaxic response, we used cDNA microarrays to identify candidate genes and assessed fly lines mutant in these genes for behavioral confirmation. We have thus determined the identities of several genes that contribute to the complex, polygenic behavior of geotaxis.

Animals↗
PubMed2002

Stress response genes protect against lethal effects of sleep deprivation in Drosophila.

Sleep is controlled by two processes: a homeostatic drive that increases during waking and dissipates during sleep, and a circadian pacemaker that controls its timing. Although these two systems can operate independently, recent studies indicate a more intimate relationship. To study the interaction between homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01)). cyc(01) mutants showed a disproportionately large sleep rebound and died after 10 hours of sleep deprivation, although they were more resistant than other clock mutants to various stressors. Unlike other clock mutants, cyc(01) flies showed a reduced expression of heat-shock genes after sleep loss. However, activating heat-shock genes before sleep deprivation rescued cyc(01) flies from its lethal effects. Consistent with the protective effect of heat-shock genes, was the observation that flies carrying a mutation for the heat-shock protein Hsp83 (Hsp83(08445)) showed exaggerated homeostatic response and died after sleep deprivation. These data represent the first step in identifying the molecular mechanisms that constitute the sleep homeostat.

ARNTL Transcription Factors↗