Internal representations of smell in the Drosophila brain

Recent advances in sensory neuroscience using Drosophila olfaction as a model system have revealed brain maps representing the external world. Once we understand how the brain's built-in capability generates the internal olfactory maps, we can then elaborate how the brain computes and makes decision to elicit complex behaviors. Here, we review current progress in mapping Drosophila olfactory circuits and discuss their relationships with innate olfactory behaviors

Human keratinocytes are vanilloid resistant

BACKGROUND: Use of capsaicin or resiniferatoxin (RTX) as analgesics is an attractive therapeutic option. RTX opens the cation channel inflammatory pain/vanilloid receptor type 1 (TRPV1) permanently and selectively removes nociceptive neurons by Ca(2+)-cytotoxicity. Paradoxically, not only nociceptors, but non-neuronal cells, including keratinocytes express full length TRPV1 mRNA, while patient dogs and experimental animals that underwent topical treatment or anatomically targeted molecular surgery have shown neither obvious behavioral, nor pathological side effects. METHODS: To address this paradox, we assessed the vanilloid sensitivity of the HaCaT human keratinocyte cell line and primary keratinocytes from skin biopsies. RESULTS: Although both cell types express TRPV1 mRNA, neither responded to vanilloids with Ca(2+)-cytotoxicity. Only ectopic overproduction of TRPV1 rendered HaCaT cells sensitive to low doses (1-50 nM) of vanilloids. The TRPV1-mediated and non-receptor specific Ca(2+)-cytotoxicity ([RTX]>15 microM) could clearly be distinguished, thus keratinocytes were indeed resistant to vanilloid-induced, TRPV1-mediated Ca(2+)-entry. Having a wider therapeutic window than capsaicin, RTX was effective in subnanomolar range, but even micromolar concentrations could not kill human keratinocytes. Keratinocytes showed orders of magnitudes lower TRPV1 mRNA level than sensory ganglions, the bona fide therapeutic targets in human pain management. In addition to TRPV1, TRPV1b, a dominant negative splice variant was also noted in keratinocytes. CONCLUSION: TRPV1B expression, together with low TRPV1 expression, may explain the vanilloid paradox: even genuinely TRPV1 mRNA positive cells can be spared with therapeutic (up to micromolar) doses of RTX. This additional safety information might be useful for planning future human clinical trials

Queen mandibular pheromone: questions that remain to be resolved

The discovery of ‘queen substance’, and the subsequent identification and synthesis of keycomponents of queen mandibular pheromone, has been of significant importance to beekeepers and to thebeekeeping industry. Fifty years on, there is greater appreciation of the importance and complexity of queenpheromones, but many mysteries remain about the mechanisms through which pheromones operate. Thediscovery of sex pheromone communication in moths occurred within the same time period, but in this case,intense pressure to find better means of pest management resulted in a remarkable focusing of research activityon understanding pheromone detection mechanisms and the central processing of pheromone signals in themoth. We can benefit from this work and here, studies on moths are used to highlight some of the gaps in ourknowledge of pheromone communication in bees. A better understanding of pheromone communication inhoney bees promises improved strategies for the successful management of these extraordinary animals

A framework for the first‑person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila

Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure-function details of the presented mechanism of perception

A Behavioral Odor Similarity “Space” in Larval Drosophila

To provide a behavior-based estimate of odor similarity in larval Drosophila, we use 4 recognition-type experiments: 1) We train larvae to associate an odor with food and then test whether they would regard another odor as the same as the trained one. 2) We train larvae to associate an odor with food and test whether they prefer the trained odor against a novel nontrained one. 3) We train larvae differentially to associate one odor with food, but not the other one, and test whether they prefer the rewarded against the nonrewarded odor. 4) In an experiment like (3), we test the larvae after a 30-min break. This yields a combined task-independent estimate of perceived difference between odor pairs. Comparing these perceived differences to published measures of physicochemical difference reveals a weak correlation. A notable exception are 3-octanol and benzaldehyde, which are distinct in published accounts of chemical similarity and in terms of their published sensory representation but nevertheless are consistently regarded as the most similar of the 10 odor pairs employed. It thus appears as if at least some aspects of olfactory perception are “computed” in postreceptor circuits on the basis of sensory signals rather than being immediately given by them

Combinatorial Activation and Repression by Seven Transcription Factors Specify Drosophila Odorant Receptor Expression

A systematic analysis reveals a regulatory network controlling selective odorant receptor expression and neuronal diversity in Drosophila

The Generation of Forces and Moments during Visual-Evoked Steering Maneuvers in Flying Drosophila

Sideslip force, longitudinal force, rolling moment, and pitching moment generated by tethered fruit flies, Drosophila melanogaster, were measured during optomotor reactions within an electronic flight simulator. Forces and torques were acquired by optically measuring the angular deflections of the beam to which the flies were tethered using a laser and a photodiode. Our results indicate that fruit flies actively generate both sideslip and roll in response to a lateral focus of expansion (FOE). The polarity of this behavior was such that the animal's aerodynamic response would carry it away from the expanding pattern, suggesting that it constitutes an avoidance reflex or centering response. Sideslip forces and rolling moments were sinusoidal functions of FOE position, whereas longitudinal force was proportional to the absolute value of the sine of FOE position. Pitching moments remained nearly constant irrespective of stimulus position or strength, with a direction indicating a tonic nose-down pitch under tethered conditions. These experiments expand our understanding of the degrees of freedom that a fruit fly can actually control in flight

Tune Deafness: Processing Melodic Errors Outside of Conscious Awareness as Reflected by Components of the Auditory ERP

Tune deafness (TD) is a central auditory processing disorder characterized by the inability to discriminate pitch, reproduce melodies or to recognize deviations in melodic structure, in spite of normal hearing. The cause of the disorder is unknown. To identify a pathophysiological marker, we ascertained a group of severely affected TD patients using the Distorted Tunes Test, an ecologically valid task with a longstanding history, and used electrophysiological methods to characterize the brain's responses to correct and incorrect melodic sequences. As expected, we identified a neural correlate of patients' unawareness of melodic distortions: deviant notes modulated long-latency auditory evoked potentials and elicited a mismatch negativity in controls but not in affected subjects. However a robust P300 was elicited by deviant notes, suggesting that, as in blindsight, TD subjects process stimuli that they cannot consciously perceive. Given the high heritability of TD, these patients may make it possible to use genetic methods to study cellular and molecular mechanisms underlying conscious awareness

Active sampling and decision making in Drosophila chemotaxis

The ability to respond to chemical stimuli is fundamental to the survival of motile organisms, but the strategies underlying odour tracking remain poorly understood. Here we show that chemotaxis in Drosophila melanogaster larvae is an active sampling process analogous to sniffing in vertebrates. Combining computer-vision algorithms with reconstructed olfactory environments, we establish that larvae orient in odour gradients through a sequential organization of stereotypical behaviours, including runs, stops, lateral head casts and directed turns. Negative gradients, integrated during runs, control the timing of turns. Positive gradients detected through high-amplitude head casts determine the direction of individual turns. By genetically manipulating the peripheral olfactory circuit, we examine how orientation adapts to losses and gains of function in olfactory input. Our findings suggest that larval chemotaxis represents an intermediate navigation strategy between the biased random walks of Escherichia Coli and the stereo-olfaction observed in rats and humans