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Radiofrequency catheter ablation of accessory pathways and modification of atrioventricular node in children and adolescents.

Catheter ablation of an accessory pathway and atrioventricular node modification using 550 kHz radiofrequency was attempted in 23 children and adolescents between five and 19 years of age (mean = 15.7 years). Fifteen children had accessory-pathway-mediated tachycardia and eight had atrioventricular node reentrant tachycardia. Accessory pathways were present in ten children. Two patients had associated congenital heart disease. Symptoms included disabling palpitations and episodes of syncope. Ablation was attempted from the right and left sides of the heart. Single-catheter technique was used in seven patients. Eleven of the 15 patients with accessory pathways were treated completely. Two patients had recurrences, and one of them died after the arrhythmia surgery. There were two failures. Two patients with incomplete interruption of the accessory pathways were followed up clinically. There were three cases with temporary systemic embolization and one with severe pain related to radiofrequency energy application. Atrioventricular node modification was done by fast-pathway ablation in six, and by slow-pathway ablation in two patients. Two patients with fast-pathway ablation had recurrences of clinical arrhythmia, and one of them underwent a successful second session. There were no complications associated with the procedure in this group of patients. Radiofrequency catheter application was initially successful in 21 (84%) out of 25 procedures, and ultimately curative in 16 (69%) out of 23 patients. There were some serious complications which resolved in the immediate post-procedure period. Radiofrequency catheter ablation appears to be a safe and successful method for the management of supraventricular tachycardia secondary to accessory pathways or atrioventricular node reentrant tachycardia in children and adolescents.

Adolescent↗

Estrogen induces axonal outgrowth in the nucleus retroambiguus-lumbosacral motoneuronal pathway in the adult female cat.

In 1995, we discovered a new pathway in the cat, which originates from the nucleus retroambiguus (NRA) and terminates in a distinct set of lumbosacral hindlimb, axial, and pelvic floor motoneuronal cell groups [VanderHorst VGJM, Holstege G (1995) Caudal medullary pathways to lumbosacral motoneuronal cell groups in the cat: evidence for direct projections possibly representing the final common pathway for lordosis. J Comp Neurol 359:457-475]. The NRA is a compact group of interneurons located laterally in the caudal medulla oblongata. Its projection to lumbosacral motoneurons is thought to represent the final common pathway for male mounting and for female receptive or lordosis behavior. However, females only display lordosis behavior. However, females only display lordosis behavior when they are in estrus, which suggests that the NRA-lumbosacral pathway is only active during estrus. This raised the question of whether estrogen affects this pathway. The effect of estrogen on the NRA-lumbosacral projection was studied light microscopically, using wheat-germ agglutinin horseradish peroxidase (WGA-HRP) as a tracer. The rubrospinal pathway served as control. The density of labeled NRA fibers in their target hindlimb motoneuronal cell groups appeared abundant in estrous and very weak in nonestrous cats. Such differences were not found in the rubrospinal pathway. For electron microscopical study, the NRA projection to the semi-membranosus motoneuronal cell group was selected. In this cell group, an almost ninefold increase of labeled profiles was found in estrous versus nonestrous cats. Moreover, the semimembranous motoneuronal cell group contained labeled growth cones in estrous, but not in nonestrous, cats. The present study is the first to show that estrogen induces axonal outgrowth of a precisely identified pathway in the adult mammalian central nervous system. The possible mechanisms underlying this outgrowth are discussed.

Animals↗

Auditory, electrosensory, and mechanosensory lateral line pathways through the forebrain in channel catfishes.

The forebrain auditory, electrosensory, and mechanosensory lateral line pathways in the channel catfish, Ictalurus punctatus, were examined by applying the fluorescent tracer DiI to 1) the auditory part of the torus semicircularis, 2) the electrosensory part of the torus semicircularis, 3) the lateral preglomerular nucleus, and 4) the anterior tuberal nucleus. Three distinct pathways ascend from the torus semicircularis to the telencephalon; they course through either 1) the lateral preglomerular nucleus of the posterior tuberculum, 2) the anterior tuberal nucleus of the hypothalamus, or 3) the central posterior nucleus of the dorsal thalamus. The anatomical data suggest that each of these ascending pathways carries information from more than one sensory modality. The lateral preglomerular nucleus receives an electrosensory input from nucleus electrosensorius in the diencephalon, but it also receives auditory and mechanosensory inputs directly from the torus semicircularis. The anterior tuberal and central posterior nuclei receive primarily auditory and mechanosensory, but also minor electrosensory, inputs. The efferent projections of the central posterior nucleus are presently unknown, but the lateral preglomerular and anterior tuberal nuclei project to nonoverlapping portions of the telencephalon. A cladistic analysis of these indirect torotelencephalic pathways reveals that 1) the pathway through the dorsal thalamus is probably a primitive character for gnathostomes, 2) a well-developed pathway through the posterior tuberculum is probably a derived character for actinopterygian fishes, 3) the pathway through nucleus electrosensorius is probably a derived character for catfishes and gymnotoid teleosts, and 4) auditory pathways through the hypothalamus probably evolved independently in catfishes and frogs.

Afferent Pathways↗

An aberrant crossed visual corticotectal pathway in albino rats.

This study investigates the dynamic nature of the developing corticotectal pathway arising in the visual cortex. Special attention is given to the interaction occurring between the corticotectal pathways of each side of the brain and between corticotectal and retinotectal terminations. Normally the visual cortex of rats projects only to the ipsilateral superior colliculus. If one visual cortex is removed at birth, the remaining visual cortex subsequently shows a bilateral projection to the superior colliculus. The aberrant corticotectal pathway is heavier if the cortical ablation is accompanied by eye removal at birth but eye enucleation alone is not a sufficient stimulus for production of a crossed corticotectal projection. The aberrant crossed pathway shows a topographic order which appears to correspond to that of the normal ipsilateral corticotectal pathway. The pathway differs from the aberrant projections from the retina in that lesions done as late as 20 days postnatal still result in an aberrant crossed corticotectal pathway. This is similar to the aberrant crossed cortical projections from sensorimotor cortex. The pathway would appear to arise as a result of lack of competition from corticotectal axons normally present contralaterally or from attraction of denervated corticotectal sites. While denervated retinotectal sites stimulate sprouting of the corticotectal axons once in the deafferented colliculus, they do not stimulate crossing of the corticotectal projection.

Age Factors↗

Complement protein C3 binding to Mycobacterium tuberculosis is initiated by the classical pathway in human bronchoalveolar lavage fluid.

In high concentrations of fresh nonimmune human serum, Mycobacterium tuberculosis activates the alternative pathway of complement and binds C3 protein, resulting in enhanced phagocytosis by complement receptors on human alveolar macrophages. Yet in the lung, the alternative pathway of complement is relatively inactive compared to the classical pathway. To begin to determine whether C3 opsonophagocytosis of M. tuberculosis by alveolar macrophages can occur in the lung of the immunologically naive host, we characterized the binding of C3 to M. tuberculosis in different concentrations of fresh nonimmune human serum and concentrated human bronchoalveolar lavage fluid. Here we show that in human serum, C3 binding to M. tuberculosis is rapid, initiated by either the alternative pathway or the classical pathway, depending on the concentration of serum, and occurs by covalent linkages between the bacterial surface and the C3 cleavage products, C3b or C3bi. Human bronchoalveolar lavage fluid contains C3 protein and functional classical pathway activity that mediates the binding of C3 to the surface of M. tuberculosis. These studies provide evidence that when M. tuberculosis is first inhaled into the lungs of the human host, the bacterium is opsonized by C3 cleavage via classical pathway activation within the alveolus, providing a C3-dependent entry pathway into resident alveolar macrophages.

Bronchoalveolar Lavage Fluid↗

MEANtools integrates multi-omics data to identify metabolites and predict biosynthetic pathways.

During evolution, plants have developed the ability to produce a vast array of specialized metabolites, which play crucial roles in helping plants adapt to different environmental niches. However, their biosynthetic pathways remain largely elusive. In the past decades, increasing numbers of plant biosynthetic pathways have been elucidated based on approaches utilizing genomics, transcriptomics, and metabolomics. These efforts, however, are limited by the fact that they typically adopt a target-based approach, requiring prior knowledge. Here, we present MEANtools, a systematic and unsupervised computational integrative omics workflow to predict candidate metabolic pathways de novo by leveraging knowledge of general reaction rules and metabolic structures stored in public databases. In our approach, possible connections between metabolites and transcripts that show correlated abundance across samples are identified using reaction rules linked to the transcript-encoded enzyme families. MEANtools thus assesses whether these reactions can connect transcript-correlated mass features within a candidate metabolic pathway. We validate MEANtools using a paired transcriptomic-metabolomic dataset recently generated to reconstruct the falcarindiol biosynthetic pathway in tomato. MEANtools correctly anticipated five out of seven steps of the characterized pathway and also identified other candidate pathways involved in specialized metabolism, which demonstrates its potential for hypothesis generation. Altogether, MEANtools represents a significant advancement to integrate multi-omics data for the elucidation of biochemical pathways in plants and beyond.

Metabolomics↗

BioEMMA: Automated Generation of Model-Specific Escher-Compatible Maps from KEGG Pathways.

Genome-scale metabolic models are widely used to investigate cellular metabolism, but their interpretation and comparison are limited by the lack of reproducible pathway-level visualizations with a common spatial organization. This study presents BioEMMA, a Python-based tool for the automated generation of model-specific metabolic pathway maps in the Escher JSON format using coordinate information from curated KEGG pathway maps. BioEMMA parses KGML files, map reaction and metabolite identifiers to model database namespaces, filters pathway elements according to an input SBML model, adds non-primary metabolites, reconstructs Escher-compatible layouts, and supports flux visualization. The tool was integrated into a reproducible BioUML workflow for metabolic model reconstruction. BioEMMA was evaluated using the e_coli_core model and the KEGG glycolysis/gluconeogenesis pathway while generating a model-specific map with overlaid FBA fluxes. It was then applied to compare E. coli reconstructions generated by gapseq, ModelSEEDpy, and Reconstructor across three central carbon metabolism pathways. To broaden the evaluation, BioEMMA was applied using 87 prokaryotic BiGG models and three eukaryotic models. The analysis revealed pathway-specific differences in reaction coverage, shared and model-specific reactions, and predicted flux activity. BioEMMA therefore provides a reproducible framework for pathway-level visualization and comparison of genome-scale metabolic reconstructions within a common spatial coordinate system.

Escher maps↗

Structural and functional characterization of complement C4 and C1s-like molecules in teleost fish: insights into the evolution of classical and alternative pathways.

There is growing evidence that certain components of complement systems in lower vertebrates are promiscuous in their modes of activation through the classical or alternative pathways. To better understand the evolution of the classical pathway, we have evaluated the degree of functional diversification of key components of the classical and alternative pathways in rainbow trout, an evolutionarily relevant teleost species. Trout C4 was purified in two distinct forms (C4-1 and C4-2), both exhibiting the presence of a thioester bond at the cDNA and protein levels. C4-1 and C4-2 bound in a similar manner to trout IgM-sensitized sheep erythrocytes in the presence of Ca(2+)/Mg(2+), and both C4 molecules equally restored the classical pathway-mediated hemolytic activity of serum depleted of C3 and C4. Reconstitution of activity was dependent on the presence of both C3-1 and C4-1/C4-2 and on the presence of IgM bound to the sheep erythrocytes. A C1s-like molecule was shown to cleave specifically purified C4-1 and C4-2 into C4b, while failing to cleave trout C3 molecules. The C1s preparation was unable to cleave trout factor B/C2 when added in the presence of C3b or C4b molecules. Our results show a striking conservation of the mode of activation of the classical pathway. We also show that functional interchange between components of the classical and alternative pathway in teleosts is more restricted than was anticipated. These data suggest that functional diversification between the two pathways must have occurred shortly after the gene duplication that gave rise to the earliest classical pathway molecules.

Amino Acid Sequence↗

Alternative pathway of complement is activated during in vitro ventricular assist.

BACKGROUND: Although ventricular assist devices (VAD) have improved survival in selected patients, their use continues to be complicated by thromboembolism and end-organ failure. Complement activation may play a role in the pathogenesis of these complications. Previous studies have found that the complement common terminal pathway is activated during VAD circulation. C3a levels rise dramatically during VAD use. Because the C3a fragment is generated by either the alternative or classical pathway, the purpose of this study is to determine the relative importance of the respective pathways in complement activation during in vitro VAD circulation. METHODS: Six in vitro VAD circuits were simulated for 3 days using 450 mL of human blood. Temperature, activated clotting time, pH, pCO2, pO2, Ca2+, and glucose were maintained at physiologic levels. Enzyme immunoassays were used to measure concentrations of fragment Bb to indicate alternative pathway activation and fragment C4d to indicate classical pathway activation. RESULTS: Fragment Bb concentrations rise from 1.92 to 10.77 micrograms/mL during the first 6 hours of circulation. Thereafter, Bb levels plateau. C4d concentrations slowly rise from a baseline of 1.49 to 6.84 micrograms/mL in 72 hours. CONCLUSIONS: These findings suggest that both the alternative and classical pathways of complement are activated during VAD circulation. Alternative pathway activation precedes classical pathway activation during in vitro VAD circulation and may be of greater clinical importance during clinical VAD circulation.

Assisted Circulation↗

Centrifugal pathways protect hearing sensitivity at the cochlea in noisy environments that exacerbate the damage induced by loud sound.

Loud sounds damage the cochlea, the auditory receptor organ, reducing hearing sensitivity. Previous studies demonstrate that the centrifugal olivocochlear pathways can moderately reduce these temporary threshold shifts (TTSs), protecting the cochlea. This effect involves only the olivocochlear pathway component known as the crossed medial olivocochlear system pathway, originating from the contralateral brainstem and terminating on outer hair cells in the cochlea. Here I demonstrate that even moderate noise backgrounds can significantly exacerbate the cochlear TTSs induced by loud tones, but this is prevented because in such conditions there is additional activation of uncrossed olivocochlear pathways, enhancing protection of cochlear hearing sensitivity. Activation of the uncrossed pathways differs from that of the crossed pathway in that it is achieved only in noise backgrounds but can then be obtained under monaural conditions of loud tone and background noise. In contrast, activation of the crossed pathway is achieved only by binaural loud tones and is not further enhanced by background noise. Thus, conjoint activation of both crossed and uncrossed efferent pathways can occur in noise backgrounds to powerfully protect the cochlea under conditions similar to those encountered naturally by humans.

Acoustic Stimulation↗

Complement pathway activity in the opsonization of mutant strains of Salmonella typhimurium.

Two separate complement pathway activities and their interaction in the opsonization of mutant strains of Salmonella typhimurium by human neutrophils were investigated in 1% and 10% sera. In the absence of antibody, all mutant strains of S. typhimurium could activate complement by either the classical or the alternative pathway. The presence of antibody did not alter alternative pathway activity but enhanced the classical pathway activity, especially for those strains possessing intact core structure and in the presence of 10% serum. This effect of antibody on classical pathway activation decreased as the lipopolysaccharide chain length decreased. The finding that the presence of antibody reduced the classical pathway activity in the opsonization of SL 1032 (Rd1) strain in 10% serum was unexpected. This suggests that if complement activity in the absence of antibody is already marked, the presence of antibody cannot increase it further. Inhibition was also found in the interaction between classical and alternative pathways. For SL 1032 (Rd1) strain, in the absence of antibody, either classical or alternative pathway activity alone could be maximally activated in 10% serum and when present together were in competition with each other. The interaction, either enhancement or inhibition, was not only dependent on the individual strain but also on the concentration of serum. In general, enhancement occurred in the presence of 1% serum while inhibition was observed in the presence of 10% serum. Such antagonistic interaction has not previously been reported.

Antibodies↗

[Role of the classical and alternative complement pathways in chemotaxis of human C2 deficiency (author's transl)].

The roles of the classical and alternative complement pathways in the formation of chemotactic factors were comparatively evaluated in a normal serum and a serum from a child with congenital C2 deficiency. Neutrophil chemotactic index was determined by a direct microscopic observation using serum activated by an immune complex for the classical pathway, and by zymosan A or liposaccharide of Salmonella enteritidis for the alternative pathway. Chemotactic activity was observed only when the C2-deficient serum was activited by the alternative pathway in the presence of zymosan A. But, in comparison to normal serum, the chemotactic activity of C2-deficient serum was impaired by dilution or short incubation time. Addition of purified C2 resulted in the normalisation of chemotactic activity induced by activation of classical and alternative pathways. These results suggest that integrity of the classical pathway of the complement is necessary for the optimal formation of the chemotactic mediators induced by the alternative complement pathway. The implications of the alternative complement pathway alteration with regard to susceptibility to bacterial infections, are discussed.

Antigen-Antibody Complex↗

Two distinct populations of tectal neurons have unique connections within the retinotectorotundal pathway of the pigeon (Columba livia).

The tectofugal pathway is a massive ascending polysynaptic pathway from the tectum to the thalamus and then to the telencephalon. In birds, the initial component of this pathway is known as the tectorotundal pathway; in mammals, it is known as the tectopulvinar pathway. The avian tectorotundal pathway is highly developed; thus, it provides a particularly appropriate model for exploring the fundamental properties of this system in all amniotes. To further define the connectivity of the tectorotundal projections of the tectofugal pathway, we injected cholera toxin B fragment into various rotundal divisions, the tectobulbar projection, and the ventral supraoptic decussation of the pigeon. We found intense bilateral retrograde labeling of neurons that stratified within layer 13 and, in certain cases, granular staining in layer 5b of the optic tectum. Based on these results, we propose that there are two distinct types of layer 13 neurons that project to the rotundus: 1) type I neurons, which are found in the outer sublamina of layer 13 (closer to layer 12) and which project to the anterior and centralis rotundal divisions, and 2) type II neurons, which are found in the inner sublamina of layer 13 (closer to layer 14) and which project to the posterior and triangularis rotundal divisions. Only the labeling of type I neurons produced the granular dendritic staining in layer 5b. An additional type of tectal neuron was also found that projected to the tectobulbar system. We then injected Phaseolus vulgaris-leucoagglutinin in the optic tract and found that the retinal axons terminating within tectal layer 5b formed narrow radial arbors (7-10 microm in diameter) that were confined to layer 5b. Based on these results, we propose that these axons are derived from a population of small retinal ganglion cells (4.5-6.0 microm in diameter) that terminate on the distal dendrites of type I neurons. This study strongly indicated the presence of a major bilateral oligosynaptic retinotectorotundal pathway arising from small retinal ganglion cells projecting to the rotundus with only a single intervening tectal neuron, the proposed type I neuron. We suggest that a similar organization of retinotectopulvinar connections exist in reptiles and in many mammals.

Afferent Pathways↗

Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation.

To gain insight into cellular and molecular mechanisms subserving neuronal cell migration in the adult mouse forebrain, we have first investigated the cellular composition of the subventricular zone-olfactory bulb pathway (SVZ-OB). The pathway was essentially composed of cells with neuronal and astrocytic identities, neuronal cells being four times more numerous than astrocytes. Neuronal cells (precursors and some young postmitotic neurons) formed continuous cellular strands of migratory cells from the anterior horn of the lateral ventricle to the olfactory bulb. These chains of migrating cells moved within channels formed by the processes of a special subpopulation of astrocytes. The neuronal cells expressed the embryonic form of polysialic acid neural cell adhesion molecule, and the astrocytes were tenascin-C positive, thus preserving an embryonic cellular environment. Through transplantation experiments, the second part of this study attempted to analyze the functional properties of the adult SVZ-OB pathway. Early postnatal (P2-13) cerebellar progenitor cells, taken from a transgenic mouse line in which cerebellar granule cells and molecular layer interneurons (basket/stellate cells) expressed the reporter gene lacZ, were implanted in the SVZ-OB pathway of adult wild-type mice. Unlike grafted SVZ cells that migrate all along the pathway, none of the cerebellar precursors reached the olfactory bulb, although some of them were able to migrate along the caudal one-third of the pathway. The majority (over 67%) of the migrating cells were progenitors that acquired the phenotype of basket/stellate cells. Granule cell progenitors and most granule cells did not survive transplantation. These results show that the adult SVZ-OB pathway is not a "passive generic guidance" for all classes of premigratory neurons. From the two types of grafted cerebellar progenitors, only those with migratory capability and that do not follow radial glial axes are able to translocate along the SVZ-OB pathway. Furthermore, the basket/stellate cell progenitors are specified at the time of grafting: Neither their identity nor the pace of expression of their major distinctive features are influenced by local signals emanating from the adult forebrain.

Animals↗

Expression of extracellular matrix molecules in the embryonic rat olfactory pathway.

Primary olfactory neurons arise from placodal neuroepithelium that is separate from the neuroepithelial plate that forms the neural tube and crest. The axons of these neurons course along a stereotypical pathway and invade the rostral telencephalic vesicle where they induce the formation of the olfactory bulb. In the present study we examined the expression of several extracellular matrix constituents during formation of the olfactory nerve pathway in order to identify putative developmentally significant molecules. Double-label immunofluorescence was used to simultaneously map the trajectory of growing primary olfactory axons by expression of growth associated protein 43 (GAP-43) and the distribution of either laminin, heparan sulfate proteoglycans (HSPG), or chondroitin sulfate proteoglycans (CSPG). At embryonic day 12.5 (E12.5) primary olfactory axons have exited the olfactory neuroepithelium of the nasal pit and formed a rudimentary olfactory nerve. These axons together with migrating neural cells form a large mass outside the rostral surface of the telencephalon. This nerve pathway is clearly defined by a punctate distribution of laminin and HSPG. CSPG is selectively present in the mesenchyme between the olfactory nerve pathway and the nasal pit and in the marginal zone of the telencephalon. At E14.5 primary olfactory axons pierce the telencephalon through gaps that have emerged in the basement membrane. At this age both laminin and HSPG are colocalized with the primary olfactory axons that have entered the marginal zone of the telencephalon. CSPG expression becomes downregulated in this same region while it remains highly expressed in the marginal zone adjacent to the presumptive olfactory bulb. By E16.5 most of the basement membrane separating the olfactory nerve from the telencephalon has degraded, and there is direct continuity between the olfactory nerve pathway and the central nervous system. This strict spatiotemporal regulation of extracellular matrix constituents in the olfactory nerve pathway supports an important role of these molecules in axon guidance. We propose that laminin and HSPG are expressed by migrating olfactory Schwann cells in the developing olfactory nerve pathway and that these molecules provide a conducive substrate for axon growth between the olfactory neuroepithelium and the brain. CSPG in the surrounding mesenchyme may act to restrict axon growth to within this pathway. The regional degradation of the basement membrane of the telencephalon and the downregulation of CSPG within the marginal zone probably facilitates the passage of primary olfactory axons into the brain to form the presumptive nerve fiber layer of the olfactory bulb.

Animals↗

Neural pathways for the control of birdsong production.

As in humans, song production in birds involves the intricate coordination of at least three major groups of muscles: namely, those of the syrinx, the respiratory apparatus, and the upper vocal tract, including the jaw. The pathway in songbirds that controls the syrinx originates in the telencephalon and projects via the occipitomesencephalic tract directly upon vocal motoneurons in the medulla. Activity in this pathway configures the syrinx into phonatory positions for the production of species typical vocalizations. Another component of this pathway mediates control of respiration during vocalization, since it projects upon both expiratory and inspiratory groups of premotor neurons in the ventrolateral medulla, as well as upon several other nuclei en route. This pathway appears to be primarily involved with the control of the temporal pattern of song, but is also importantly involved in the control of vocal intensity, mediated via air sac pressure. There are extensive interconnections between the vocal and respiratory pathways, especially at brain-stem levels, and it may be these that ensure the necessary temporal coordination of syringeal and respiratory activity. The pathway mediating control of the jaw appears to be different from those mediating control of the syrinx and respiratory muscles. It originates in a different part of the archistriatum and projects upon premotor neurons in the medulla that appear to be separate from those projecting upon the syringeal motor nucleus. The separateness of this pathway may reflect the imperfect correlation of jaw movements with the dynamic and acoustic features of song. The brainstem pathways mediating control of vocalization and respiration in songbirds have distinct similarities to those in mammals such as cats and monkeys. However, songbirds, like humans, but unlike most other non-songbirds, have developed a telencephalic vocal control system for the production of learned vocalizations.

Animals↗

Systematic analysis of the visual projection neurons of Drosophila melanogaster. I. Lobula-specific pathways.

In insects, visual information is processed in the optic lobe and conveyed to the central brain. Although neural circuits within the optic lobe have been studied extensively, relatively little is known about the connection between the optic lobe and the central brain. To understand how visual information is read by the neurons of the central brain, and what kind of centrifugal neurons send the control signal from the central brain to the optic lobe, we performed a systematic analysis of the visual projection neurons that connect the optic lobe and the central brain of Drosophila melanogaster. By screening approximately 4,000 GAL4 enhancer-trap strains we identified 44 pathways. The overall morphology and the direction of information of each pathway were investigated by expressing cytoplasmic and presynapsis-targeted fluorescent reporters. A canonical nomenclature system was introduced to describe the area of projection in the central brain. As the first part of a series of articles, we here describe 14 visual projection neurons arising specifically from the lobula. Eight pathways form columnar arborization in the lobula, whereas the remaining six form tangential or tree-like arborization. Eleven are centripetal pathways, among which nine terminate in the ventrolateral protocerebrum. Terminals of each columnar pathway form glomerulus-like structures in different areas of the ventrolateral protocerebrum. The posterior lateral protocerebrum and the optic tubercle were each contributed by a single centripetal pathway. Another pathway connects the lobula on each side of the brain. Two centrifugal pathways convey signals from the posterior lateral protocerebrum to the lobula.

Animals↗

Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat.

Stimulation of the dorsomedial or ventrolateral perforant pathways resulted in quantitatively different extracellularly recorded EPSPs in the fascia dentata of the rat. The two potentials differed in latency to peak and in width at half amplitude in a manner consistent with the different locus of termination of the two pathways on the granule cell dendrites. Both potentials were able to follow brief stimulus trains of 100 Hz, which suggests that they are monosynaptic. Medially elicited responses had their peak negativity approximately 100 to 180 micrometer deeper in the molecular layer than laterally elicited responses. Stimulation at short intervals along a dorsomedial to ventrolateral track in the angular bundle yielded a step function rather than a continuum of EPSP peak latency and half-width, in agreement with Hjorth-Simonsen's ('72) evidence for the separateness of the two pathways. Both pathways were able to induce granule cell discharge. Laterally elicited spikes, however, were delayed. Stimulation at intermediate locations frequently elicited double spikes from the granule cell population. Population spikes elicited by either pathway were inhibited for as long as 100 msec after a single discharge. Both pathways showed facilitation with double stimuli at short intervals, and both showed post-tetanic potentiation lasting at least 30 minutes. Under conditions where it could be shown that the two pathways at least partially converged onto the same granule cells, the response of one pathway did not increase when long lasting potentiation was induced on the other.

Animals↗