My goal is to understand the neural circuits underlying taste perception in the fly brain. The Drosophila gustatory system is an excellent model for the study of sensory perception because it is associated with well-defined taste ligands, robust behavioral responses, and a complex nervous system that is amenable to molecular, genetic, and functional approaches. Our previous studies have led to the identification of different classes of taste neurons and elucidated the map of different taste modalities in the primary gustatory region of the fly brain. Understanding how taste information is processed higher in the brain to produce perception and behavior will require a comprehensive anatomical and functional analysis of fly taste circuits. Taste circuits may then provide a template on which to map additional complex problems, such as experiential learning and sensory integration. Our three immediate and long-term goals are to (1) determine how taste information is detected in the periphery, (2) identify higher-order taste circuits to examine sensory processing in the brain, and (3) examine how taste circuits and behaviors are modified by experience.
Taste Detection in the Periphery
Sensory neurons detect features in the outside world and translate them into a neural code that is converted by the brain into perception and behavior. The features that the fly taste system detects are the quality and the position of a chemical compound. To define the sensory information detected and processed by the taste system, we are determining the number and molecular basis of different taste qualities, as well as the degree of positional information represented in sensory neurons and their projections.
Our previous studies identified three taste cell populations that detect different taste categories, including the tastes of sugars, bitter compounds, and carbon dioxide, but at least two taste cell populations remain uncharacterized. We have performed microarray analyses to enrich for genes that are expressed in taste organs but not other tissues. These studies, and subsequent in situ hybridization and transgenic analyses, have identified several taste neuron–specific genes, some that label new taste neuron populations and some that may be involved in the detection of specific tastes. We are combining molecular, genetic, and calcium-imaging approaches to determine the function of these molecules, and we are characterizing the response properties of taste neurons that express them. These studies will identify taste modalities in Drosophila and characterize novel molecular mechanisms for taste detection that may be relevant to mammals.
Higher-Order Taste Processing
How the brain processes sensory information to produce behavior is largely unknown. Currently, little is known about fly taste circuits, except that sensory neurons, motor neurons driving proboscis extension and feeding, and candidate modulatory neurons arborize in the subesophageal ganglion (SOG). It is interesting to speculate that simple circuits mediating taste reflexes might be localized to the SOG, but that in addition, communication between gustatory circuits and higher brain centers may allow for more complex taste associations. To understand how taste information is processed in the fly, it is necessary to identify taste neural circuits with cellular resolution. The molecular genetic approaches available in the fly to label, activate, and silence neurons, as well as the ability to monitor neural activity and assay neural involvement in behavior, allow the dissection of neuronal circuits to a degree difficult to achieve in mammals.
We are performing experiments to identify taste neural circuits. Our aim is to determine the selectivity of higher-order neurons and assess whether there is segregation or integration of taste quality and intensity in different brain regions. To identify neurons involved in taste processing, we have performed a genetic screen in which we have conditionally silenced random neurons in the fly brain and examined the effect on taste behavior. In a screen of several hundred Gal enhancer traplines expressed in the brain, we have identified fly lines that do not detect bitter compounds, other lines that do not detect sugars, and some with defects in proboscis extension. To identify higher-order taste neurons, we are determining the neurons causal for the behavioral defects. In addition, we are using more directed approaches to isolate synaptic partners of different classes of gustatory neurons and proboscis motor neurons. These studies will advance our long-term goal of understanding taste encoding in the brain.
Modulation of Taste Circuits and Behavior
For an animal to survive in a constantly changing environment, its behavior must be shaped by the complex milieu of sensory stimuli it detects, its previous experience, and its internal state. Although taste behaviors in the fly are relatively simple, with sugars mediating acceptance behavior and bitter compounds mediating avoidance, these behaviors are also plastic and modified by intrinsic and extrinsic cues. A long-term goal is to examine how taste activity in the brain is modified to allow for behavioral plasticity. Two modulations that we are studying are the modulation of taste behavior by hunger and satiety and modulation by associative learning. We have established behavioral assays to examine taste plasticity, and we are performing studies to determine the brain regions involved. We are also studying molecular mechanisms underlying the regulation of feeding behavior. These studies will provide insight into the degree of behavioral plasticity and discrimination in the fly taste system. The long-term value of these paradigms is that they will facilitate examining neural mechanisms governing behavioral plasticity.
Grants from the National Institutes of Health and the John Merck Fund provided partial support for these projects.
As of May 30, 2012