Modeling the Influence of Ion Channels on Neuron Dynamics in Drosophila.

Voltage gated ion channels play a major role in determining a neuron's firing behavior, resulting in the specific processing of synaptic input patterns. Drosophila and other invertebrates provide valuable model systems for investigating ion channel kinetics and their impact on firing properties. Despite the increasing importance of Drosophila as a model system, few computational models of its ion channel kinetics have been developed. In this study, experimentally observed biophysical properties of voltage gated ion channels from the fruitfly Drosophila melanogaster are used to develop a minimal, conductance based neuron model. We investigate the impact of the densities of these channels on the excitability of the model neuron. Changing the channel densities reproduces different in situ observed firing patterns and induces a switch from integrator to resonator properties. Further, we analyze the preference to input frequency and how it depends on the channel densities and the resulting bifurcation type the system undergoes. An extension to a three dimensional model demonstrates that the inactivation kinetics of the sodium channels play an important role, allowing for firing patterns with a delayed first spike and subsequent high frequency firing as often observed in invertebrates, without altering the kinetics of the delayed rectifier current.

Relating ion channel expression, bifurcation structure, and diverse firing patterns in a model of an identified motor neuron.

Neurons show diverse firing patterns. Even neurons belonging to a single chemical or morphological class, or the same identified neuron, can display different types of electrical activity. For example, motor neuron MN5, which innervates a flight muscle of adult Drosophila, can show distinct firing patterns under the same recording conditions. We developed a two-dimensional biophysical model and show that a core complement of just two voltage-gated channels is sufficient to generate firing pattern diversity. We propose Shab and DmNa v to be two candidate genes that could encode these core currents, and find that changes in Shab channel expression in the model can reproduce activity resembling the main firing patterns observed in MN5 recordings. We use bifurcation analysis to describe the different transitions between rest and spiking states that result from variations in Shab channel expression, exposing a connection between ion channel expression, bifurcation structure, and firing patterns in models of membrane potential dynamics.

Creating, documenting and sharing network models.

As computational neuroscience matures, many simulation environments are available that are useful for neuronal network modeling. However, methods for successfully documenting models for publication and for exchanging models and model components among these projects are still under development. Here we briefly review existing software and applications for network model creation, documentation and exchange. Then we discuss a few of the larger issues facing the field of computational neuroscience regarding network modeling and suggest solutions to some of these problems, concentrating in particular on standardized network model terminology, notation, and descriptions and explicit documentation of model scaling. We hope this will enable and encourage computational neuroscientists to share their models more systematically in the future.

The auditory system of non-calling grasshoppers (Melanoplinae: Podismini) and the evolutionary regression of their tympanal ears.

Reduction of tympanal hearing organs is repeatedly found amongst insects and is associated with weakened selection for hearing. There is also an associated wing reduction, since flight is no longer required to evade bats. Wing reduction may also affect sound production. Here, the auditory system in four silent grasshopper species belonging to the Podismini is investigated. In this group, tympanal ears occur but sound signalling does not. The tympanal organs range from fully developed to remarkably reduced tympana. To evaluate the effects of tympanal regression on neuronal organisation and auditory sensitivity, the size of wings and tympana, sensory thresholds and sensory central projections are compared. Reduced tympanal size correlates with a higher auditory threshold. The threshold curves of all four species are tuned to low frequencies with a maximal sensitivity at 3-5 kHz. Central projections of the tympanal nerve show characteristics known from fully tympanate acridid species, so neural elements for tympanal hearing have been strongly conserved across these species. The results also confirm the correlation between reduction in auditory sensitivity and wing reduction. It is concluded that the auditory sensitivity of all four species may be maintained by stabilising selective forces, such as predation.

Unraveling the genetic complexity of Drosophila stardust during photoreceptor morphogenesis and prevention of light-induced degeneration.

Drosophila Stardust, a membrane-associated guanylate kinase (MAGUK), recruits the transmembrane protein Crumbs and the cytoplasmic proteins DPATJ and DLin-7 into an apically localized protein scaffold. This evolutionarily conserved complex is required for epithelial cell polarity in Drosophila embryos and mammalian cells in culture. In addition, mutations in Drosophila crumbs and DPATJ impair morphogenesis of photoreceptor cells (PRCs) and result in light-dependent retinal degeneration. Here we show that stardust is a genetically complex locus. While all alleles tested perturb epithelial cell polarity in the embryo, only a subset of them affects morphogenesis of PRCs or induces light-dependent retinal degeneration. Alleles retaining particular postembryonic functions still express some Stardust protein in pupal and/or adult eyes. The phenotypic complexity is reflected by the expression of distinct splice variants at different developmental stages. All proteins expressed in the retina contain the PSD95, Discs Large, ZO-1 (PDZ), Src homology 3 (SH3), and guanylate kinase (GUK) domain, but lack a large region in the N terminus encoded by one exon. These results suggest that Stardust-based protein scaffolds are dynamic, which is not only mediated by multiple interaction partners, but in addition by various forms of the Stardust protein itself.

Honey bees navigate according to a map-like spatial memory.

By using harmonic radar, we report the complete flight paths of displaced bees. Test bees forage at a feeder or are recruited by a waggle dance indicating the feeder. The flights are recorded after the bees are captured when leaving the hive or the feeder and are released at an unexpected release site. A sequence of behavioral routines become apparent: (i) initial straight flights in which they fly the course that they were on when captured (foraging bees) or that they learned during dance communication (recruited bees); (ii) slow search flights with frequent changes of direction in which they attempt to "get their bearings"; and (iii) straight and rapid flights directed either to the hive or first to the feeding station and then to the hive. These straight homing flights start at locations all around the hive and at distances far out of the visual catchment area around the hive or the feeding station. Two essential criteria of a map-like spatial memory are met by these results: bees can set course at any arbitrary location in their familiar area, and they can choose between at least two goals. This finding suggests a rich, map-like organization of spatial memory in navigating honey bees.

Enhancement of equine infectious anemia virus virulence by identification and removal of suboptimal nucleotides.

Pathogenicity was reportedly restored to an avirulent molecular clone of equine infectious anemia virus (EIAV) by substitution of 3' sequences from the pathogenic variant strain (EIAV(PV)). However, the incidence of disease in horses/ponies was found to be significantly lower (P = 0.016) with the chimeric clone (EIAV(UK)) than with EIAV(PV). This was attributable to 3' rather than 5' regions of the proviral genome, where EIAV(UK) differs from the consensus EIAV(PV) sequence by having a 68-bp duplication in the 3' LTR and arginine (R(103)) rather than tryptophan (W(103)) at position 103 in the second exon of rev. In EIAV(UK) recipients the duplication was rapidly eliminated and R(103) replaced by W(103) in the viral population. Furthermore, removal of the 3' variant sequences from EIAV(UK) (EIAV(UK3)) resulted in an equivalent (P = 0.013) disease potential in Equus caballus to EIAV(PV). The 68-bp duplication and/or R(103) may limit peak viral RNA accumulation during acute infection.