Neurofly 2008 abstracts : the 12th European Drosophila neurobiology conference 6-10 September 2008 Wuerzburg, Germany

This volume consists of a collection of conference abstracts

A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Event Timing in Associative Learning

Associative learning relies on event timing. Fruit flies for example, once trained with an odour that precedes electric shock, subsequently avoid this odour (punishment learning); if, on the other hand the odour follows the shock during training, it is approached later on (relief learning). During training, an odour-induced Ca++ signal and a shock-induced dopaminergic signal converge in the Kenyon cells, synergistically activating a Ca++-calmodulin-sensitive adenylate cyclase, which likely leads to the synaptic plasticity underlying the conditioned avoidance of the odour. In Aplysia, the effect of serotonin on the corresponding adenylate cyclase is bi-directionally modulated by Ca++, depending on the relative timing of the two inputs. Using a computational approach, we quantitatively explore this biochemical property of the adenylate cyclase and show that it can generate the effect of event timing on associative learning. We overcome the shortage of behavioural data in Aplysia and biochemical data in Drosophila by combining findings from both systems

Maintenance of cell type-specific connectivity and circuit function requires Tao kinase

Sensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. To gain insight we quantitatively investigated synaptic growth and connectivity in the Drosophila nociceptive network during larval development. We show that connectivity between primary nociceptors and their downstream neurons scales with animal size. We further identified the conserved Ste20-like kinase Tao as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity. Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. Using functional imaging and behavioral analysis we show that loss of Tao-induced ectopic synapses with inappropriate partner neurons are functional and alter behavioral responses in a connection-specific manner. Our data show that fine-tuning of synaptic growth by Tao kinase is required for maintaining specificity and behavioral output of the neuronal network during animal growth

Sex differences in behavioral decision-making and the modulation of shared neural circuits

Animals prioritize behaviors according to their physiological needs and reproductive goals, selecting a single behavioral strategy from a repertoire of possible responses to any given stimulus. Biological sex influences this decision-making process in significant ways, differentiating the responses animals choose when faced with stimuli ranging from food to conspecifics. We review here recent work in invertebrate models, including C. elegans, Drosophila, and a variety of insects, mollusks and crustaceans, that has begun to offer intriguing insights into the neural mechanisms underlying the sexual modulation of behavioral decision-making. These findings show that an animal's sex can modulate neural function in surprisingly diverse ways, much like internal physiological variables such as hunger or thirst. In the context of homeostatic behaviors such as feeding, an animal's sex and nutritional status may converge on a common physiological mechanism, the functional modulation of shared sensory circuitry, to influence decision-making. Similarly, considerable evidence suggests that decisions on whether to mate or fight with conspecifics are also mediated through sex-specific neuromodulatory control of nominally shared neural circuits. This work offers a new perspective on how sex differences in behavior emerge, in which the regulated function of shared neural circuitry plays a crucial role. Emerging evidence from vertebrates indicates that this paradigm is likely to extend to more complex nervous systems as well. As men and women differ in their susceptibility to a variety of neuropsychiatric disorders affecting shared behaviors, these findings may ultimately have important implications for human health

Dissecting the mechanisms of learning-by-doing in Drosophila

At the heart of learning-by-doing lies a well-known psychological phenomenon: information will be remembered better if it is actively generated rather than passively read or heard. First described in humans, this generation effect can also be observed in various animal models. However, the neurobiological mechanisms underlying the generation effect are unknown. Here we show that two reciprocal interactions between its active and passive components contribute to the generation effect in flies. One interaction consists of the active (skill-learning) component facilitating the passive (fact-learning) component. Fact-learning, on the other hand, inhibits skill-learning. Experiments with adenylyl cyclase I deficient _rutabaga_ mutant flies revealed that the fact- but not the skill-learning component requires this evolutionarily conserved learning gene. Using mushroom-body deficient transgenic flies we observed that the mushroom-bodies mediate the inhibition of skill-learning. This inhibition also enables generalization and prevents premature habit formation. Extended training in wildtype flies produced a phenocopy of mushroom-body impaired flies, such that generalization was abolished and goal-directed actions were transformed into habitual responses. Thus, our results identify various neural processes underlying learning-by-doing, delineate some of their synergisms and provide a framework for further dissecting them in a genetically tractable model system

Circuit motifs for sensory integration, learning, and the initiation of adaptive behavior in Drosophila

Goal-directed behavior is crucial for survival in complex, dynamic environments. It requires the detection of relevant sensory stimuli and the formation of separable neuronal representations. Learning the contingencies of these sensory stimuli with innately positive or negative valent stimuli (reinforcement) forms associations, allowing the former to cue the latter. This yields cue-based predictions to upgrade the behavioral repertoire from reactive to anticipatory. In this thesis, the Trias of sensory integration, learning of contingencies, and the initiation of anticipatory behavior are studied in the framework of the fruit fly Drosophila olfactory pathway and mushroom body, a higher-order brain center for integrating sensory input and coincidence detection using computational network models representing the mushroom body architecture with varying degrees of abstraction. Additionally, simulations of larval locomotion were employed to investigate how the output of the mushroom body relates to behavior and to foster comparability with animal experiments. We showed that inhibitory feedback within the mushroom body produces sparse stimulus representations, increasing the separability of different sensory stimuli. This separability reduced reinforcement generalization in learning experiments through the decreased overlap of stimulus representations. Furthermore, we showed that feedback from the valence-signaling output to the reinforcement-signaling dopaminergic neurons that innervate the mushroom body could explain experimentally observed temporal dynamics of the formation of associations between sensory cues and reinforcement. This supports the hypothesis that dopaminergic neurons encode the difference between predicted and received reinforcement, which in turn drives the learning process. These dopaminergic neurons have also been argued to convey an indirect reinforcement signal in second-order learning experiments. A new sensory cue is paired with an already established one that activates dopaminergic neurons due to its association with the reinforcement. We demonstrated how different pathways for feedforward or feedback input from the mushroom body’s intrinsic or output neurons can provide an indirect reinforcement signal to the dopaminergic neurons. Any direct or indirect association of sensory cues with reinforcement yielded a reinforcement expectation, biasing the fly’s behavioral response towards the approach or avoidance of the respective sensory cue. We then showed that the simulated locomotory behavior of individual animals in a virtual environment depends on the biasing output of the mushroom body. In conclusion, our results contribute to understanding the implementation of mechanisms for separable stimulus representations, postulated key features of associative learning, and the link between MB output and adaptive behavior in the mushroom body and confirm their explanatory power for animal behavior