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R F Stocker

Publications and source records attributed to R F Stocker.

At least 19 recordsLinked to original sources

Visual learning in individually assayed Drosophila larvae.

An understanding of associative learning is facilitated if it can be analyzed in a simple animal like the fruit fly Drosophila. Here, we introduce the first visual associative learning paradigm for larval Drosophila; this is remarkable as larvae have an order of magnitude fewer neurons than adult flies. Larvae were subjected to either of two reciprocal training regimes: Light+/Dark- or Light-/Dark+. Subsequently, all larvae were individually tested for their preference between Light versus Dark. The difference between training regimes was therefore exclusively which visual situation was associated with which reinforcer; differences observed during the test thus reflected exclusively associative learning. For positive reinforcement (+) we used fructose (FRU), and for negative reinforcement (-) either quinine or sodium chloride (QUI, NaCl). Under these conditions, associative learning could be reproducibly observed in both wild-type strains tested. We then compared the effectiveness of training using differential conditioning, with both positive and negative reinforcement, to that using only positive or only negative reinforcement. We found that FRU only, but neither QUI nor NaCl, was in itself effective as a reinforcer. This is the first demonstration of appetitive learning in larval Drosophila. It is now possible to investigate the behavioral and neuronal organization of appetitive visual learning in this simple and genetically easy-to-manipulate experimental system.

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A central neural circuit for experience-independent olfactory and courtship behavior in Drosophila melanogaster.

We have studied the function of the major central olfactory pathway in fruit flies. Key elements of this pathway, the projection neurons (PNs), connect the antennal lobes with the lateral protocerebrum both directly and indirectly, the latter via the mushroom bodies (MBs). Transgenic expression of tetanus toxin in the majority of PNs and few MB neurons leads to defects in odor detection and male courtship. Considering behavioral data from flies lacking MBs, our results argue that the direct PN-to-lateral protocerebrum pathway is necessary and sufficient to process these experience-independent behaviors. Moreover, the involvement of an olfactory pathway in male courtship suggests a role of volatile attractive female pheromones in Drosophila.

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Drosophila as a focus in olfactory research: mapping of olfactory sensilla by fine structure, odor specificity, odorant receptor expression, and central connectivity.

This review intends to integrate recent data from the Drosophila olfactory system into an up-to-date account of the neuronal basis of olfaction. It focuses on (1) an electron microscopic study that mapped a large proportion of fruitfly olfactory sensilla, (2) large-scale electrophysiological recordings that allowed the classification of the odor response spectra of a complete set of sensilla, (3) the identification and expression patterns of candidate odorant receptors in the olfactory tissues, (4) central projections of neurons expressing a given odorant receptor, (5) an improved glomerular map of the olfactory center, and (6) attempts to exploit the larval olfactory system as a model of reduced cellular complexity. These studies find surprising parallels between the olfactory systems of flies and mammals, and thus underline the usefulness of the fruitfly as an olfactory model system. Both in Drosophila and in mammals, odorant receptor neurons appear to express only one type of receptor. Neurons expressing a given receptor are scattered in the olfactory tissues but their afferents converge onto a few target glomeruli only. This suggests that in both phyla, the periphery is represented in the brain as a chemotopic map. The major difference between mammals and fruitflies refers to the numbers of receptors, neurons, and glomeruli, which are largely reduced in the latter, and particularly in larvae. Yet, if activated in a combinatorial fashion, even this small set of elements could allow discrimination between a vast array of odorants.

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Target neuron prespecification in the olfactory map of Drosophila.

In Drosophila and mice, olfactory receptor neurons (ORNs) expressing the same receptors have convergent axonal projections to specific glomerular targets in the antennal lobe/olfactory bulb, creating an odour map in this first olfactory structure of the central nervous system. Projection neurons of the Drosophila antennal lobe send dendrites into glomeruli and axons to higher brain centres, thereby transferring this odour map further into the brain. Here we use the MARCM method to perform a systematic clonal analysis of projection neurons, allowing us to correlate lineage and birth time of projection neurons with their glomerular choice. We demonstrate that projection neurons are prespecified by lineage and birth order to form synapses with specific incoming ORN axons, and therefore to carry specific olfactory information. This prespecification could be used to hardwire the fly's olfactory system, enabling stereotyped behavioural responses to odorants. Developmental studies lead us to hypothesize that recognition molecules ensure reciprocally specific connections of ORNs and projection neurons. These studies also imply a previously unanticipated role for precise dendritic targeting by postsynaptic neurons in determining connection specificity.

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The genetic variant Voila causes gustatory defects during Drosophila development.

Voila(1), an enhancer-trap strain in Drosophila melanogaster, expresses GAL4 in most gustatory neurons, both before and after metamorphosis. Voila(1) expression starts at embryonic stage 10. In the periphery, it labels larval gustatory sensilla in the antennomaxillary complex as well as in the pharynx. GAL4 is also expressed in the CNS in a manner that prefigures expression in adult flies. Most Voila(1/1) homozygotes die between second larval instar and early adulthood. Moreover, escaping Voila(1/1) larvae do not show gustatory responses to NaCl and sucrose. The simultaneous rescue of normal larval gustation together with adult viability after removal of the transposable PGAL4 element suggests that both these phenotypes are caused by the same inserted element.

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Metamorphosis in drosophila and other insects: the fate of neurons throughout the stages.

The nervous system of insects is profoundly reorganised during metamorphosis, affecting the fate of different types of neuron in different ways. Almost all adult motor neurons derive from larval motor neurons that are respecified for adult functions. A subset of larval motor neurons, those which mediate larval- or ecdysis-specific behaviours, die before and immediately after eclosion, respectively. Many adult interneurons develop from larval interneurons, whereas those related to complex adult sense organs originate during larval life from persisting embryonic neuroblasts. Sensory neurons of larvae and adults derive from essentially two distinct sources. Larval sensory neurons are formed in the embryonic integument and - with few exceptions - die during metamorphosis. Their adult counterparts, on the other hand, arise from imaginal discs. Special emphasis is given in this review to the metamorphic remodelling of persisting neurons, both at the input and output levels, and to the associated behavioural changes. Other sections deal with the programmed death of motor neurons and its causes, as well as with the metamorphic interactions between motor neurons and their target muscles. Remodelling and apoptosis of these two elements appear to be under independent ecdysteroid control. This review focusses on the two most thoroughly studied holometabolous species, the fruitfly Drosophila melanogaster and the tobacco hornworm moth Manduca sexta. While Manduca has a long tradition in neurodevelopmental studies due to the identification of many of its neurons, Drosophila has been increasingly used to investigate neural reorganisation thanks to neurogenetic tools and molecular approaches. The wealth of information available emphasises the strength of the insect model system used in developmental studies, rendering it clearly the most important system for studies at the cellular level.

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Binding sites of Drosophila melanogaster sex peptide pheromones.

Drosophila melanogaster sex peptide (SP) and Ductus ejaculatorius peptide (DUP99B) are male pheromones transferred in the seminal fluid to the female during copulation. Both reduce sexual receptivity and stimulate oviposition in females. The presence of high-affinity SP and DUP99B binding sites in the female were investigated by incubation of cryostat tissue sections with (125)I-iodinated peptides and subsequent autoradiography. We found that in adult females radiolabeled SP and DUP99B bind to peripheral nerves, the subesophageal ganglion, the cervical connective, to discrete parts of the thoracic ganglion, and to the genital tract. Weak and uniform labeling was detected in the neuropil of the brain and the thoracic ganglion. The labeling pattern in the nervous system suggests binding of the peptides to sensory afferents or glial cells. Scatchard analysis of the binding of (125)I-DUP99B to antennal nerves yielded a dissociation constant K(d) of 6.4 nM. Competition experiments with peptide fragments show that the peptides bind with their homologous C-terminal regions. Binding sites in the nervous system of females are established throughout sexual maturation. Prominent binding of the peptides to afferent nerves suggests modification of sensory input.

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Smell and taste perception in Drosophila melanogaster larva: toxin expression studies in chemosensory neurons.

GAL4-driven targeted expression of tetanus toxin light chain (UAS-TeTxLC) in a subset of chemosensory neurons of the larval antennomaxillary complex (AMC) and pharynx causes abnormal chemosensory behavior in Drosophila melanogaster. Consistent with strongest staining in the dorsal organ (DO), the presumed olfactory organ of the AMC, tetanus toxin-expressing larvae subjected to an olfactory preference assay show anosmic behavior to most volatile substances tested. Furthermore, we observed reduced responses to sodium chloride, fructose, and sucrose in gustatory plate assays. Surprisingly, the entire subset of labeled sensory neurons from the terminal (maxillary) organ (TO) of the AMC was found to project via the antennal nerve to the larval antennal lobe region. The maxillary nerve remained completely unstained. Hence, a subset of neurons from the TO builds an anatomical entity with projections from the DO. Our results suggest that the AMC contains both olfactory and gustatory sensilla, and that the DO is the main olfactory organ in larvae.

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Three-dimensional reconstruction of the antennal lobe in Drosophila melanogaster.

We present the first three-dimensional map of the antennal lobe of Drosophila melanogaster, based on confocal microscopic analysis of glomeruli stained with the neuropil-specific monoclonal antibody nc82. The analysis of confocal stacks allowed us to identify glomeruli according to the criteria shape, size, position, and intensity of antibody labeling. Forty glomeruli were labeled by nc82, eight of which have not been described before. Three glomeruli previously shown exclusively by backfills were not discernible in nc82 stainings. We distinguish three classes of glomeruli: (1) "landmark" glomeruli that are constant in all four criteria mentioned above, (2) less well-demarcated glomeruli that deviate in a single criterion, and (3) poorly defined glomeruli that vary in more than one criterion. All class 2 and 3 glomeruli can be identified by comparison with landmark neighbors. To further aid identification, our model assigns glomeruli to five arrays, each of which is defined by a prominent landmark glomerulus. Six glomeruli consist of distinct, but contiguous structural units, termed "compartments." Glomerular variability observed occasionally between males and females is in the same range as between individuals of the same sex, suggesting the lack of a significant sexual dimorphism in the glomerular pattern. We compare the new model with a previous map and address its potential for mapping activity and expression patterns. An important goal of this work was to create three-dimensional reference models of the antennal lobe, which are accessible on-line.

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Drosophila P[Gal4] lines reveal that motor neurons involved in feeding persist through metamorphosis.

Two P[Gal4] insertion lines in Drosophila melanogaster, MT11 and MT26, express GAL4 specifically in two to three pairs of pharyngeal motor neurons (PMN) in the suboesophageal ganglion. By using various secondary reporters, the architecture of the PMN, including their efferent axons in the pharyngeal nerve, was visualized. This allowed us to identify a pharyngeal dilator muscle as their target. To study the function of these neurons, we crossed line MT11 with a UAS-tetanus toxin gene construct (TNT-C) that inhibits all synaptic transmission. The offspring shows a reduction in food ingestion of 75% compared to the MT11 and TNT-C controls, demonstrating that PMN control food uptake. More important, lines MT11 and MT26 enabled us to follow PMN and their processes through metamorphosis, since labeling appears in the late third larval instar and persists up to adulthood. The motor axons innervate a pharyngeal muscle in the larva as well and extend through the maxillary nerve, proving that this nerve is homologous to the adult pharyngeal nerve. Efferent arborizations persist throughout metamorphosis, even though the larval muscle histolyzes by 20% of pupal life. Yet, some dedifferentiated structures remain, which may serve as a template for the formation of the adult muscle. Labeling of line MT26 with bromodeoxyuridine at embryonic or larval stages suggests that these neurons undergo their terminal mitosis in the mid to late embryo.

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Voila, a new Drosophila courtship variant that affects the nervous system: behavioral, neural, and genetic characterization.

In Drosophila melanogaster, a specific PGAL4 transposon induces the Voila1 genetic variant and produces multiple phenotypes. Homozygous Voila1/1 flies rarely reach adulthood, whereas heterozygous Voila1/+ adult males show strong bisexual behavior. Males with a single copy of Voila1 driving the feminizing transgene UAS-transformer show very reduced sexual activity but no overall effect on their behavior. Voila1 is specifically expressed in the nervous system. In the CNS, it is expressed mainly in the mushroom bodies and, to a lesser extent, in the antennal lobes. In the peripheral nervous system, GAL4 expression is almost entirely restricted to the gustatory sensilla. Using chromosomal deficiencies, the behavioral alteration was genetically mapped to the same location as the PGAL4 element (86E1-2). The multiple behavioral effects of the Voila genetic variant are discussed in light of its expression in the nervous system and its genetic basis.

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Larval chemosensory projections and invasion of adult afferents in the antennal lobe of Drosophila.

We have studied the fate of olfactory afferents during metamorphic transformation of Drosophila melanogaster. Intracellular labeling of afferents from larval head chemosensilla suggests that the larval antennal lobe may be an olfactory target, whereas tritocerebral and suboesophageal centers are likely targets of gustatory sensilla. Application of monoclonal antibody 22C10 shows that the larval antennal nerve is the precursor of the adult antennal nerve and is used as a centripetal pathway for the adult afferents. Likely guidance cues are larval olfactory afferents that persist during early metamorphosis. P[GAL4] enhancer trap lines are introduced as efficient markers to follow the establishment of adult sensory projection. beta-Galactosidase and the bovine TAU protein were used as reporter proteins, and their expression patterns are compared. P[GAL4] lines MT14 and KL116 demonstrate that adult antennal afferents have arrived in the antennal lobe 24 h after pupariation and extend to the contralateral lobe 6 h later. Line MT14 expresses GAL4 mostly in basiconic sensilla and in certain trichoid sensilla, whereas KL116 is specific for trichoid and a small subset of basiconic sensilla. In the antennal lobe, largely complementary subsets of glomeruli are labeled by the two lines, in agreement with the observation that particular types of sensilla project to particular target glomeruli.

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Neuroblast ablation in Drosophila P[GAL4] lines reveals origins of olfactory interneurons.

Hydroxyurea (HU) treatment of early first instar larvae in Drosophila was previously shown to ablate a single dividing lateral neuroblast (LNb) in the brain. Early larval HU application to P[GAL4] strains that label specific neuron types enabled us to identify the origins of the two major classes of interneurons in the olfactory system. HU treatment resulted in the loss of antennal lobe local interneurons and of a subset of relay interneurons (RI), elements usually projecting to the calyx and the lateral protocerebrum (LPR). Other RI were resistant to HU and still projected to the LPR. However, they formed no collaterals in the calyx region (which was also ablated), suggesting that their survival does not depend on targets in the calyx. Hence, the ablated interneurons were derived from the LNb, whereas the HU-resistant elements originated from neuroblasts which begin to divide later in larval life. Developmental GAL4 expression patterns suggested that differentiated RI are present at the larval stage already and may be retained through metamorphosis.

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Genetic analysis of the lozenge gene complex in Drosophila melanogaster: adult visual system phenotypes.

Mutations at the lozenge (lz) locus are pleiotropic, primarily affecting the sense organs for sight, smell and taste. To better understand the role that lz plays in the visual system, we investigated its complex genetics and the effect mutations have on the structure of the compound eye. Complementation analysis within the lz locus reveals two functional units necessary for a normal eye, cistrons A and B. Previous recombination studies identified four subloci spanning 0.14 m.u. Cistron A mutations map to the distal-most spectacle sub-locus, which has been identified as an insertion point for P-elements. Southern blotting and chromosomal in situ hybridization show that P-allele lzmu2 contains a single P-element; a cosmid clone derived from lzmu2 confirms that the P-element is defective. Mutants of both cistrons perturb lens structure and eye pigmentation. However, the extent of the defects differs between the most severe mutations of the two cistrons. Within the eye, failure to form the fenestrated membrane permits photoreceptor neurons to "fall" into the brain disrupting neural structure. Our analysis shows that lz exerts control over the identity of cone cells, pigment cells and photoreceptor neurons.

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Genetic feminization of brain structures and changed sexual orientation in male Drosophila.

The neural basis of sexual orientation in Drosophila was studied by the production of males with regionally feminized brains. Such flies express the female form of the sex determination gene transformer in a limited number of neurons under the control of GAL4 enhancer trap inserts. This method facilitated the creation of lines with a stable pattern of feminization. In tests of sexual preferences, flies that were feminized in a portion of the antennal lobes or in a subset of the corpora pedunculata (mushroom bodies) courted both males and females. These two brain structures, both of which are involved in olfactory processing, may function in the recognition of sex-specific pheromones, in the control of sex-specific behaviors, or both.

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The organization of the chemosensory system in Drosophila melanogaster: a review.

This review surveys the organization of the olfactory and gustatory systems in the imago and in the larva of Drosophila melanogaster, both at the sensory and the central level. Olfactory epithelia of the adult are located primarily on the third antennal segment (funiculus) and on the maxillary palps. About 200 basiconic (BS), 150 trichoid (TS) and 60 coeloconic sensilla (CS) cover the surface of the funiculus, and an additional 60 BS are located on the maxillary palps. Males possess about 30% more TS but 20% fewer BS than females. All these sensilla are multineuronal; they may be purely olfactory or multimodal with an olfactory component. Antennal and maxillary afferents converge onto approximately 35 glomeruli within the antennal lobe. These projections obey precise rules: individual fibers are glomerulus-specific, and different types of sensilla are associated with particular subsets of glomeruli. Possible functions of antennal glomeruli are discussed. In contrast to olfactory sensilla, gustatory sensilla of the imago are located at many sites, including the labellum, the pharynx, the legs, the wing margin and the female genitalia. Each of these sensory sites has its own central target. Taste sensilla are usually composed of one mechano- and three chemosensory neurons. Individual chemosensory neurons within a sensillum respond to distinct subsets of molecules and project into different central target regions. The chemosensory system of the larva is much simpler and consists essentially of three major sensillar complexes on the cephalic lobe, the dorsal, terminal and ventral organs, and a series of pharyngeal sensilla.

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Analysis of immunocytochemical staining patterns in the antennal system of Drosophila melanogaster.

By immunizing mice with homogenized brains, heads, or a mixture of heads and antennae of D. melanogaster, we obtained six monoclonal antibodies (mabs) that bind to the olfactory system of Drosophila with various degrees of specificity. They can be divided into three groups with respect to their staining pattern: (1) The antibodies ca51/2, na21/2, and nb230 label both in the third (olfactory) antennal segment and in the visual ganglia. All of them bind to antennal structures that can be correlated with basiconic sensilla. The antibody ca51/2 labels sensory neurons of these sensilla. In the antenna of the lozenge mutant, which lacks basiconic sensilla, no labeling is present. In Western blots ca51/2 recognizes in the antenna an antigen of 43.5 kDa, which is expressed in the antenna only in the presence of basiconic sensilla. The antibody na21/2 binds to basiconic and coeloconic sensilla, most likely to the apical part of sheath cells. In immunoblots it recognizes in the antenna two antigens of 42.2 kDa and 46.7 kDa. The latter appears to be correlated in the antenna with the presence of basiconic sensilla. (2) The staining pattern of antibody nc10 is associated with the sheath cells of basiconic and coeloconic sensilla. Moreover, nc10 binds to a subset of glomeruli in the antennal lobe. (3) The staining pattern of the antibodies VG2 and I24B5 is restricted to the antenna. I24B5 recognizes coeloconic sensilla and VG2 recognizes both coeloconic and basiconic sensilla. Staining patterns in both cases include sheath cells.

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Analysis of the antennal phenotype in the Drosophila mutant lozenge.

Previous work on the lozenge (lz) gene complex of D. melanogaster has focused on the compound eye. Here we study the effects of 22 lz mutations on the antennal sensilla. The antenna of strong lz alleles is characterized by a lack of basiconic sensilla and by a significantly increased density of coeloconic sensilla. Intermediate alleles have few basiconic sensilla, they exhibit a highly increased density of trichoid sensilla, but a normal coeloconic density. Basiconic sensilla on the maxillary palps are weakly affected even by strong lz alleles. The antennal phenotype for most of the strong and intermediate mutants is partially dominant over wild type. Although this complicates the interpretation of complementation data, 12 selected mutants that were studied in heteroallelic combinations seem to define a single cistron. Temperature shifts of the lztsl allele showed that gene activity is crucial from about 87% of the third larval instar up to 7% of pupal life. Applying restrictive temperature early during this period results in a 'novel' phenotype that is characterized by a dramatic decrease in the density of trichoid sensilla, whereas a late pulse of restrictive temperature leads to a 'normal' intermediate phenotype. Our data suggest that the lz gene controls at least five different functions in the antenna: the size of the third antennal segment, the overall number and density of sensilla, the proportions of the 3 types of sensilla, and the generation of basiconic sensilla.

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