20 research outputs found
Neural mechanisms underlying memory in drosophila melanogaster
No full textIn a complex and constantly changing environment, animals are required to guide behaviour in a dynamic way to adapt to the current environment as well as the organism’s needs. Although the ability to remember past events allows animals to predict future outcomes and thereby guide behaviour, an input does not always produce stereotypical behaviours. Factors such as conflicting information from parallel memories, cue specificity and context will impact the predictability of an outcome across time. Similarly, the animal’s internal state influences whether the predicted outcome should be pursued at a given moment. Moreover, biological relevance of the memory, such as nutrient-reinforced associations, are thought to affect the lability of the memory and therefore how accessible it will be. Integration of predictability, motivation and memory stability allows a dynamic retrieval of appropriate memories to guide behaviour to properly balance their internal state.
Previous research in Drosophila has yielded detailed mechanisms describing the neural circuitry and molecular correlates involved in memory processing, but we lack a full understanding of how factors affecting memory retrieval become integrated to produce changes in behaviour. The work presented throughout this thesis uses Drosophila melanogaster to investigate the neuronal and behavioural mechanisms and how these factors regulate behavioural outcomes across time. In this work, repeated stimulus presentations were used to address how stimulus exposure prior to learning affects the formation and expression of new memories across time. Our results show that odour pre-exposure leads to an aversive memory which competes with subsequently acquired memories, leading to latent inhibition of memory expression. Changes in context between pre-exposure and testing allow conflict resolution, retrieval of the appropriate trained memory and inhibition of pre-exposure memory.
The second experimental chapter examines nutrient-reinforced long-term memory and the dynamics of its retrieval across time. Interestingly, neuronal stimulation studies have suggested that emergence of long-term nutrient-reinforced memory is independent of short-term memory, suggesting a delayed association between stimuli and nutrient-reward. However, the results presented here suggest that this apparent emergent memory results from an inhibition of short-term memory, potentially due to a motivational switch produced by co-activation of retrieval-inhibiting neurons. Taken together, the work presented throughout this thesis delves into how different mechanisms, from memory integration to motivational suppression and context, lead to a temporal inhibition of memory retrieval to shape a changing behaviour across time
Genetic approaches in Drosophila for the study neurodevelopmental disorders
No full textThe fruit fly Drosophila melanogaster is one of the premier genetic model organisms used in biomedical research today owing to the extraordinary power of its genetic tool-kit. Made famous by numerous seminal discoveries of basic developmental mechanisms and behavioral genetics, the power of fruit fly genetics is becoming increasingly applied to questions directly relevant to human health. In this review we discuss how Drosophila research is applied to address major questions in neurodevelopmental disorders. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.status: Publishe
Twists to classical conditioning of adult drosophila
No full textMemory has been extensively studied in Drosophila since the early 1970s. Straightforward aversive and appetitive conditioning paradigms train populations of flies to associate the pairing of one of two odors with either punishment or reward. After training, the flies show either preferential avoidance or approach behavior, to the appropriate odor, when given a choice between the two odors in a simple T-maze apparatus. These basic experimental approaches have proven useful in understanding the genetic, molecular, cellular, and neuronal network bases of various valence-specific memories in the fly brain. In addition, numerous modifications to these assays have permitted the study of a broad range of memory-related phenomena. Labile short-term avoidance and approach memories can be readily distinguished from more stable "consolidated" long-term memory equivalents. Prior or subsequent experience of the training cues, and manipulations of the flies' condition, have revealed how parallel competing memories and incompatible states can temporarily interfere with memory retrieval, providing insight into mechanisms of forgetting. Recent studies have also modified the training and testing apparatus to allow simultaneous presentation of odors and colors, providing insight into mechanisms of multisensory learning
Investigation of TAT and Rorschach Responses of Males Who are Facing with Male Factor Infertility
No full textNarratives about infertility, diagnosis and treatment interferences are as old as human history. The review of infertility literature showed that the main object of infertility were women and as usual male infertility kept as an hidden subject. In literature male factor infertility studied in physiological aspects and psychological aspects of it somehow denied. The aim of this is to evaluate two cases with projective techniques (Rorschach Test and TAT-Thematic Apperception Test) in order to see their psychic organizations about infertility. The main findings of the study were the identifications, differences between sexes, and also transgenerational differences could not be clearly identified. The responses to these two projective techniques can be identified as more immature and infanlite althoug their are adults. In other words more infantile identification was made by cases. In both cases, the mother/woman was considered to be as an omnipotent being and on the other hand devalued at the same time which can be considered as ambivalance towards mother/woman. The wording and phrases that are used by these two cases containts too much hesitations and repeteaded words which can be evaluated as immaturity. Both of the cases do not form a relationship neither with the clinician nor the test material which can be evaluated as a defence mechanism upon both the outer and ther inner world. This study is considered to be an important contribution to the literature because it is the first study conducted -with the knowledge of author- upon male factor infertility
The Drosophila homologue of the amyloid precursor protein is a conserved modulator of Wnt PCP signaling
No full textWnt Planar Cell Polarity (PCP) signaling is a universal regulator of polarity in epithelial cells, but it regulates axon outgrowth in neurons, suggesting the existence of axonal modulators of Wnt-PCP activity. The Amyloid precursor proteins (APPs) are intensely investigated because of their link to Alzheimer's disease (AD). APP's in vivo function in the brain and the mechanisms underlying it remain unclear and controversial. Drosophila possesses a single APP homologue called APP Like, or APPL. APPL is expressed in all neurons throughout development, but has no established function in neuronal development. We therefore investigated the role of Drosophila APPL during brain development. We find that APPL is involved in the development of the Mushroom Body αβ neurons and, in particular, is required cell-autonomously for the β-axons and non-cell autonomously for the α-axons growth. Moreover, we find that APPL is a modulator of the Wnt-PCP pathway required for axonal outgrowth, but not cell polarity. Molecularly, both human APP and fly APPL form complexes with PCP receptors, thus suggesting that APPs are part of the membrane protein complex upstream of PCP signaling. Moreover, we show that APPL regulates PCP pathway activation by modulating the phosphorylation of the Wnt adaptor protein Dishevelled (Dsh) by Abelson kinase (Abl). Taken together our data suggest that APPL is the first example of a modulator of the Wnt-PCP pathway specifically required for axon outgrowth
Reduced Lateral Inhibition Impairs Olfactory Computations and Behaviors in a Drosophila Model of Fragile X Syndrome
No full textInternational audienceFragile X syndrome (FXS) patients present neuronal alterations that lead to severe intellectual disability, but the underlying neuronal circuit mechanisms are poorly understood. An emerging hypothesis postulates that reduced GABAergic inhibition of excitatory neurons is a key component in the pathophysiology of FXS. Here, we directly test this idea in a FXS Drosophila model. We show that FXS flies exhibit strongly impaired olfactory behaviors. In line with this, olfactory representations are less odor specific due to broader response tuning of excitatory projection neurons. We find that impaired inhibitory interactions underlie reduced specificity in olfactory computations. Finally, we show that defective lateral inhibition across projection neurons is caused by weaker inhibition from GABAergic interneurons. We provide direct evidence that deficient inhibition impairs sensory computations and behavior in an in vivo model of FXS. Together with evidence of impaired inhibition in autism and Rett syndrome, these findings suggest a potentially general mechanism for intellectual disability
Prior experience conditionally inhibits the expression of new learning in Drosophila
No full textPrior experience of a stimulus can inhibit subsequent acquisition or expression of a learned association of that stimulus. However, the neuronal manifestations of this learning effect, named latent inhibition (LI), are poorly understood. Here, we show that prior odor exposure can produce context-dependent LI of later appetitive olfactory memory performance in Drosophila. Odor pre-exposure forms a short-lived aversive memory whose lone expression lacks context-dependence. Acquisition of odor pre-exposure memory requires aversively reinforcing dopaminergic neurons that innervate two mushroom body compartments—one group of which exhibits increasing activity with successive odor experience. Odor-specific responses of the corresponding mushroom body output neurons are suppressed, and their output is necessary for expression of both pre-exposure memory and LI of appetitive memory. Therefore, odor pre-exposure attaches negative valence to the odor itself, and LI of appetitive memory results from a temporary and context-dependent retrieval deficit imposed by competition with the parallel short-lived aversive memory
Classical conditioning of adult drosophila
No full textOlfactory classical conditioning paradigms have been extensively used since the early 1970s to apply genetic approaches to the study of memory in Drosophila. Over the intervening years, advances in genetics have largely changed the focus of studies from the role of single genes in memory to investigation of memory-relevant neuronal circuits. However, the original behavioral paradigms have remained largely unaltered, besides investigators making a few useful tweaks to the training and testing apparatus and modifications to the operating procedures. In this protocol, we provide the reader with a detailed description of the manufacture and assembly of a typical T-maze apparatus, where populations of adult flies can be trained and their odor memory tested later, by giving them a binary choice between the two trained odors. We describe how variations of the training apparatus permit both aversive (odor-shock) and appetitive (odor-sugar) memories to be studied. In addition, we describe a recent modification of the apparatus and protocol that permits study of multisensory (color and odor) aversive and appetitive learning. Control assays for sensory acuity and locomotion are also included
Multisensory learning binds neurons into a cross-modal memory engram
No full textAssociating multiple sensory cues with objects and experience is a fundamental brain process that improves object recognition and memory performance. However, neural mechanisms that bind sensory features during learning and augment memory expression are unknown. Here we demonstrate multisensory appetitive and aversive memory in Drosophila. Combining colours and odours improved memory performance, even when each sensory modality was tested alone. Temporal control of neuronal function revealed visually selective mushroom body Kenyon cells (KCs) to be required for enhancement of both visual and olfactory memory after multisensory training. Voltage imaging in head-fixed flies showed that multisensory learning binds activity between streams of modality-specific KCs so that unimodal sensory input generates a multimodal neuronal response. Binding occurs between regions of the olfactory and visual KC axons, which receive valence-relevant dopaminergic reinforcement, and is propagated downstream. Dopamine locally releases GABAergic inhibition to permit specific microcircuits within KC-spanning serotonergic neurons to function as an excitatory bridge between the previously ‘modality-selective’ KC streams. Cross-modal binding thereby expands the KCs representing the memory engram for each modality into those representing the other. This broadening of the engram improves memory performance after multisensory learning and permits a single sensory feature to retrieve the memory of the multimodal experience
