Emulation of chemical stimulus triggered head movement in the C. elegans nematode

For a considerable time, it has been the goal of computational neuroscientists to understand biological nervous systems. However, the vast complexity of such systems has made it very difficult to fully understand even basic functions such as movement. Because of its small neuron count, the C. elegans nematode offers the opportunity to study a fully described connectome and attempt to link neural network activity to behaviour. In this paper a simulation of the neural network in C. elegans that responds to chemical stimulus is presented and a consequent realistic head movement demonstrated. An evolutionary algorithm (EA) has been utilised to search for estimates of the values of the synaptic conductances and also to determine whether each synapse is excitatory or inhibitory in nature. The chemotaxis neural network was designed and implemented, using the parameterization obtained with the EA, on the Si elegans platform a state-of-the-art hardware emulation platform specially designed to emulate the C. elegans nematode

Microfluidic Devices and Systems for Neuroscience Studies in Caenorhabditiselegans (C. elegans).

C. elegans, a tiny, transparent roundworm with a simple nervous system (302 neurons) and a diverse repertoire of behavioral outputs, has been extensively used as a model organism in neuroscience. Its optically accessible, compact nervous system offers a unique advantage for understanding the ability of the nervous system to compute various behaviors of an organism. C. elegans, however poses a challenge as a model organism – due to its small size (1 mm in length and 40 – 50 µm in diameter), conducting experimental procedures on the worm is skill-intensive and time consuming. To this end, microfluidic technology has recently emerged as a preferred tool for conducting experimental procedures on the worm and this thesis contributes towards the development of such microfluidic approaches. We demonstrated the design and development of microfluidic devices and systems that serve the following applications : a) Immobilization - We developed two microfluidic approaches for immobilizing C. elegans on-chip. These approaches are easy to implement, allow worm recovery within a few seconds after immobilization and can be easily adopted for conducting cell developmental and neuron regeneration studies in C. elegans. b) Calcium Imaging - We developed an automated microfluidic platform for collecting stimulus-evoked calcium imaging data from single neurons. We utilized the platform to monitor neuronal activity in the chemosensory neuron - ASH - in response to different stimuli (chemical and electrical) and characterized its dependence on the age of the worm. The platform enabled us to hypothesize that the neuronal functionality is altered with age. We believe that the use of microfluidic devices will allow the observation of large scale neuronal dynamics in C. elegans. Consequently, we foresee the use of computational procedures for uncovering new insights about the worm’s nervous system. To this end, we propose a hardware based computational platform for emulating the worm’s nervous system. And, as a step towards this futuristic goal, we present an analog circuit that emulates the observed ASH neuronal activity in C. elegans. We envision that the work demonstrated in this thesis will expand the toolsets available for conducting neuroscience studies in C. elegans.Ph.D.Electrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/89766/1/tchokshi_1.pd

線虫の塩走化性回路を制御する神経活動に関する研究

筑波大学 (University of Tsukuba)201

Activation of the pro-resolving receptor Fpr2 attenuates inflammatory microglial activation

Poster number: P-T099 Theme: Neurodegenerative disorders & ageing Activation of the pro-resolving receptor Fpr2 reverses inflammatory microglial activation Authors: Edward S Wickstead - Life Science & Technology University of Westminster/Queen Mary University of London Inflammation is a major contributor to many neurodegenerative disease (Heneka et al. 2015). Microglia, as the resident immune cells of the brain and spinal cord, provide the first line of immunological defence, but can become deleterious when chronically activated, triggering extensive neuronal damage (Cunningham, 2013). Dampening or even reversing this activation may provide neuronal protection against chronic inflammatory damage. The aim of this study was to determine whether lipopolysaccharide (LPS)-induced inflammation could be abrogated through activation of the receptor Fpr2, known to play an important role in peripheral inflammatory resolution. Immortalised murine microglia (BV2 cell line) were stimulated with LPS (50ng/ml) for 1 hour prior to the treatment with one of two Fpr2 ligands, either Cpd43 or Quin-C1 (both 100nM), and production of nitric oxide (NO), tumour necrosis factor alpha (TNFα) and interleukin-10 (IL-10) were monitored after 24h and 48h. Treatment with either Fpr2 ligand significantly suppressed LPS-induced production of NO or TNFα after both 24h and 48h exposure, moreover Fpr2 ligand treatment significantly enhanced production of IL-10 48h post-LPS treatment. As we have previously shown Fpr2 to be coupled to a number of intracellular signaling pathways (Cooray et al. 2013), we investigated potential signaling responses. Western blot analysis revealed no activation of ERK1/2, but identified a rapid and potent activation of p38 MAP kinase in BV2 microglia following stimulation with Fpr2 ligands. Together, these data indicate the possibility of exploiting immunomodulatory strategies for the treatment of neurological diseases, and highlight in particular the important potential of resolution mechanisms as novel therapeutic targets in neuroinflammation. References Cooray SN et al. (2013). Proc Natl Acad Sci U S A 110: 18232-7. Cunningham C (2013). Glia 61: 71-90. Heneka MT et al. (2015). Lancet Neurol 14: 388-40

25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Interspecific competition between the potato cyst nematode species Globodera pallida and G. rostochiensis

The two potato cyst nematode species, Globodera pallida and G. rostochiensis, are among the most important pests of potato. PCN are difficult to manage, while the two species respond differently to the main control methods. An increase in the incidence of G. pallida had been reported and is generally attributed to greater effectiveness of control measures against G. rostochiensis. The status of PCN in Ireland was studied using PCR. The results demonstrated qPCR to be an efficient means of high-throughput PCN sampling, being able to accurately identify both species in mixed-species populations. Species discrimination using qPCR revealed an increase in the incidence of G. pallida in Ireland in the absence of G. pallida-selective control measures. The population dynamics of G. pallida and G. rostochiensis in Ireland were studied in mixed- and single-species competition assays in vivo. G. pallida proved to be the more successful species, with greater multiplication in mixed- than single-species populations, with G. rostochiensis showing the opposite. This effect was similarly observed in staggered inoculation trials and population proportion trials. It was hypothesised that the greater G. pallida competitiveness could be attributed to its later hatch. G. pallida exhibited a later peak in hatching activity and more prolonged hatch, relative to G. rostochiensis. G. rostochiensis hatch was significantly reduced in mixedspecies hatching assays. G. pallida hatch was significantly higher when hatch was induced in potato root leachates containing G. rostochiensis-specific compounds, indicating that G. pallida hatch is stimulated upon perception of G. rostochiensis–derived compounds. Rhizotron studies revealed that root damage, caused by feeding of the early-hatching G. rostochiensis, resulted in increased lateral root proliferation and significantly increased G. pallida multiplication. Split-root trials indicated a significant G. pallida-induced ISR effect. G. rostochiensis multiplication was significantly reduced in split-root rhizotrons when G. pallida colonised roots before or after G. rostochiensis infection