Troy Zars

Distinct memory traces for two visual features in the Drosophila brain

The fly Drosophila melanogaster can discriminate and remember visual landmarks. It analyses selected parts of its visual environment according to a small number of pattern parameters such as size, colour or contour orientation, and stores particular parameter values. Like humans, flies recognize patterns independently of the retinal position during acquisition of the pattern (translation invariance). Here we show that the central-most part of the fly brain, the fan-shaped body, contains parts of a network mediating visual pattern recognition. We have identified short-term memory traces of two pattern parameters—elevation in the panorama and contour orientation. These can be localized to two groups of neurons extending branches as parallel, horizontal strata in the fan-shaped body. The central location of this memory store is well suited to mediate translational invariance.

Serotonin is necessary for place memory in Drosophila

Biogenic amines, such as serotonin and dopamine, can be important in reinforcing associative learning. This function is evident as changes in memory performance with manipulation of either of these signals. In the insects, evidence begins to argue for a common role of dopamine in negatively reinforced memory. In contrast, the role of the serotonergic system in reinforcing insect associative learning is either unclear or controversial. We investigated the role of both of these signals in operant place learning in Drosophila. By genetically altering serotonin and dopamine levels, manipulating the neurons that make serotonin and dopamine, and pharmacological treatments we provide clear evidence that serotonin, but not dopamine, is necessary for place memory. Thus, serotonin can be critical for memory formation in an insect, and dopamine is not a universal negatively reinforcing signal.

Behavioral functions of the insect mushroom bodies.

New methods of intervention in Drosophila and other insect species reveal that the mushroom bodies are involved in a diverse set of behavioral functions. The intrinsic Kenyon cells (those neurons with projections within the mushroom bodies) house part of the short-term memory trace for odors and are required for courtship conditioning memory. A pair of extrinsic mushroom body neurons (neurons with projections both inside and outside the mushroom bodies) provides a neuropeptide important for 1-hour olfactory memory. In addition, the mushroom bodies are necessary for context generalization in visual learning and for regulating the transition from walking to rest.

Learning and Memory in Drosophila: Behavior, Genetics, and Neural Systems

The rich behavioral repertoire that Drosophila use to navigate in their natural environment suggests that flies can use memories to inform decisions. Development of paradigms to examine memories that restrict behavioral choice was essential in furthering our understanding of the genetics and neural systems of memory formation in the fly. Olfactory, visual, and place memory paradigms have proven influential in determining principles for the mechanisms of memory formation. Several parts of the nervous system have been shown to be important for different types of memories, including the mushroom bodies and the central complex. Thus far, about 40 genes have been linked to normal olfactory short-term memory. A subset of these genes have also been tested for a role in visual and place memory. Some genes have a common function in memory formation, specificity of action comes from where in the nervous system these genes act. Alternatively, some genes have a more restricted role in different types of memories.

Two thermosensors in Drosophila have different behavioral functions.

Abstract. Insects inhabit extreme temperature environments and have evolved mechanisms to survive there. Small insects are especially susceptible to rapid changes in body temperature. Therefore, the rapid detection of environment and body temperature is important for their survival. Little, however, is known about the thermosensors that detect those temperatures. Using rapid thermosensitivity assays with temperature step gradients and a spatial learning paradigm (the heat-box) in which elevated temperature serves as the negative reinforcer, two thermosensors were identified and their behavioral functions assessed. A low-temperature thermosensor is located on the antenna, detects relatively low temperatures, and can detect spatial temperature gradients directly. Thus, the antennae can be used by Drosophila to quickly orient with respect to temperature cues. A high-temperature thermosensor of unknown location appears to have a roughly similar sensitivity to temperature differences as the low-temperature thermosensor (≤3°C) and is both necessary and sufficient for memory formation in the heat-box spatial learning paradigm. Therefore, the high-temperature thermosensor is important for remembering spatial positions in which dangerously high temperatures were encountered.

Serotonin is Critical for Rewarded Olfactory Short-Term Memory in Drosophila

Abstract: The biogenic amines dopamine, octopamine, and serotonin are critical in establishing normal memories. A common view for the amines in insect memory performance has emerged in which dopamine and octopamine are largely responsible for aversive and appetitive memories. Examination of the function of serotonin begins to challenge the notion of one amine type per memory because altering serotonin function also reduces aversive olfactory memory and place memory levels. Could the function of serotonin be restricted to the aversive domain, suggesting a more specific dopamine/serotonin system interaction? The function of the serotonergic system in appetitive olfactory memory was examined. By targeting the tetanus toxin light chain (TNT) and the human inwardly rectifying potassium channel (Kir2.1) to the serotonin neurons with two different GAL4 driver combinations, the serotonergic system was inhibited. Additional use of the GAL80ts1 system to control expression of transgenes to the adult stage of the life cycle addressed a potential developmental role of serotonin in appetitive memory. Reduction in appetitive olfactory memory performance in flies with these transgenic manipulations, without altering control behaviors, showed that the serotonergic system is also required for normal appetitive memory. Thus, serotonin appears to have a more general role in Drosophila memory, and implies an interaction with both the dopaminergic and octopaminergic systems.

Short-term memories in Drosophila are governed by general and specific genetic systems

In a dynamic environment, there is an adaptive value in the ability of animals to acquire and express memories. That both simple and complex animals can learn is therefore not surprising. How animals have solved this problem genetically and anatomically probably lies somewhere in a range between a single molecular/anatomical mechanism that applies to all situations and a specialized mechanism for each learning situation. With an intermediate level of nervous system complexity, the fruit fly Drosophila has both general and specific resources to support different short-term memories. Some biochemical/cellular mechanisms are common between learning situations, indicating that flies do not have a dedicated system for each learning context. The opposite possible extreme does not apply to Drosophila either. Specialization in some biochemical and anatomical terms suggests that there is not a single learning mechanism that applies to all conditions. The distributed basis of learning in Drosophila implies that these systems were independently selected.

Spatial orientation in Drosophila

Abstract: Spatial orientation is critical for many behaviors. Intrinsic to the oriented state is the knowledge of past, present, and future spatial location relative to one or more landmarks. How do animals so fluidly solve this problem? Determining mechanisms of orientation may benefit from investigation of relatively simple organisms. Two behaviors that presumably use path integration as a major input to orientation—place learning and persistent target selection—allow for the examination of cellular and neural circuit mechanisms in Drosophila. Although our understanding of these processes is still relatively immature, some recent findings provide insights into the mechanisms supporting orientation. First, place learning provides good access to the past, present, and future aspects of orientation, but currently is less open to understanding how a fly establishes a relationship to landmarks. The change in behavior after learning is orientation away from, and avoiding, a place predicted to punish a fly, incorporating all temporal aspects of orientation, and can last for minutes to hours. This conclusion is supported by several learning phenomena. Second, persistent target selection provides the best access to the processes determining relationships to landmarks. Using a disappearing visual-landmark paradigm, persistent target selection was shown to require parts of the central complex for a seconds-long “path integration memory.” How the path integration memory, on this short time scale, is related to longer lasting place memories is, as yet, unknown. Nevertheless, studies of place learning and persistent target selection may provide insights into orientation mechanisms in a simple brain.

High and low temperatures have unequal reinforcing properties in Drosophila spatial learning

Small insects regulate their body temperature solely through behavior. Thus, sensing environmental temperature and implementing an appropriate behavioral strategy can be critical for survival. The fly Drosophila melanogaster prefers 24°C, avoiding higher and lower temperatures when tested on a temperature gradient. Furthermore, temperatures above 24°C have negative reinforcing properties. In contrast, we found that flies have a preference in operant learning experiments for a low-temperature-associated position rather than the 24°C alternative in the heat-box. Two additional differences between high- and low-temperature reinforcement, i.e., temperatures above and below 24°C, were found. Temperatures equally above and below 24°C did not reinforce equally and only high temperatures supported increased memory performance with reversal conditioning. Finally, low- and high-temperature reinforced memories are similarly sensitive to two genetic mutations. Together these results indicate the qualitative meaning of temperatures below 24°C depends on the dynamics of the temperatures encountered and that the reinforcing effects of these temperatures depend on at least some common genetic components. Conceptualizing these results using the Wolf–Heisenberg model of operant conditioning, we propose the maximum difference in experienced temperatures determines the magnitude of the reinforcement input to a conditioning circuit.

Place memory formation in Drosophila is independent of proper octopamine signaling.

The biogenic amines play a critical role in establishing memories. In the insects, octopamine, dopamine, and serotonin have key functions in memory formation. For Drosophila, octopamine is necessary and sufficient for appetitive olfactory memory formation. Whether octopamine plays a general role in reinforcing memories in the fly is not known. Place learning in the heat-box associates high temperatures with one part of a narrow chamber, and a cool, strongly preferred temperature with the other half of the chamber. The cool-temperature-associated chamber half could provide a rewarding stimulus to a fly, and thus a place memory is composed of an aversive and rewarded memory component. The role of octopamine in place memory was thus tested. Using a mutation in the tyramine beta hydroxylase (TβH[M18]) and blocking of evoked synaptic transmission in the octopamine (and tyramine) neurons labeled with a tyramine decarboxylase-2 (TDC2) gene regulatory elements we found that reinforcement of place memories is independent of normal octopamine signaling. Thus, reinforcing mechanisms in Drosophila have specialized systems in the formation of specific memory types.