CAIRN Research Ltd.

Faversham, United Kingdom

CAIRN Research Ltd.

Faversham, United Kingdom
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Busch K.E.,Medical Research Council Laboratory of Molecular Biology | Laurent P.,Medical Research Council Laboratory of Molecular Biology | Soltesz Z.,Medical Research Council Laboratory of Molecular Biology | Murphy R.J.,Medical Research Council Laboratory of Molecular Biology | And 5 more authors.
Nature Neuroscience | Year: 2012

Tonic receptors convey stimulus duration and intensity and are implicated in homeostatic control. However, how tonic homeostatic signals are generated and how they reconfigure neural circuits and modify animal behavior is poorly understood. Here we show that Caenorhabditis elegans O 2-sensing neurons are tonic receptors that continuously signal ambient [O 2[ to set the animal's behavioral state. Sustained signaling relied on a Ca 2+ relay involving L-type voltage-gated Ca 2+ channels, the ryanodine and the inositol-1,4,5-trisphosphate receptors. Tonic activity evoked continuous neuropeptide release, which helps elicit the enduring behavioral state associated with high [O 2[. Sustained O 2 receptor signaling was propagated to downstream neural circuits, including the hub interneuron RMG. O 2 receptors evoked similar locomotory states at particular O 2 concentrations, regardless of previous d[O 2[/dt. However, a phasic component of the URX receptors' response to high d[O 2[/dt, as well as tonic-to-phasic transformations in downstream interneurons, enabled transient reorientation movements shaped by d[O 2[/dt. Our results highlight how tonic homeostatic signals can generate both transient and enduring behavioral change. © 2012 Nature America, Inc. All rights reserved.


Grant
Agency: GTR | Branch: BBSRC | Program: | Phase: Research Grant | Award Amount: 109.76K | Year: 2011

Much of what we know about how cells function, how they communicate and process information and how they transport essential elements and molecules has come from the application of electrophysiological approaches. The most well known example of this is the pioneering work of Hodgkin and Huxley, carried out at the Marine Biological Association (MBA) with the giant nerve fibre of the squid which led to the discovery of how nerve cells transmit impulses and formed the basis of much modern neurobiology. Since these seminal discoveries the field of electrophysiology has expanded dramatically and electrophysiological approaches are applied to study a wide range of processes in cells, including the functional characterization of molecules that are increasingly being characterised at the molecular level. In 1984 it was decided that there was a need for an annual research workshop to provide training in the varied uses of microelectrode techniques. This has proven to be a very valuable contribution to cell biology and biophysics and has had significant impact on the training of new generations of cell physiologists. The MBA was chosen as the venue for this workshop since it provided both excellent workshop facilities and a continuing tradition of microelectrode and associated biophysical approaches in cell biology. The workshop has continued uninterrupted since then and is now recognised worldwide as one of the leading advanced research workshops in this field. The need to train the new generation of electrophysiolgists continues, particularly with the increased emphasis on functional characterisation of membrane proteins and a wide range of cell biological areas. The workshop continues to be over-subscribed with applications 3-4 fold each year for the 20 places available. To meet this continuing need the proposed 5-year extension to the ongoing workshop will provide training in both the basic principles and more advanced practical and theoretical aspects of electrophysiology. New approaches are planned to be incorporated over this period. The basic workshop fomat will continue with a core of teaching and demonstrating staff recruited mainly from research laboratories in the UK and Europe along with an intensive series of talks and demonstrations from invited international experts. The workshop also benefits from the good relations that have been established over 28 years with a large number of commercial instrument manufacturers that ensures significant in-kind contributions of equipment and who also contribute expertise as instructors.


Davies R.,CAIRN Research Ltd | Graham J.,CAIRN Research Ltd | Canepari M.,French Institute of Health and Medical Research | Canepari M.,Joseph Fourier University | Canepari M.,Laboratories of Excellence Ion Channel Science and Therapeutics
Journal of Microscopy | Year: 2013

Membrane potential and fast ion imaging are now standard optical techniques routinely used to record dynamic physiological signals in several preparations in vitro. Although detailed resolution of optical signals can be improved by confocal or two-photon microscopy, high spatial and temporal resolution can be obtained using conventional microscopy and affordable light sources and cameras. Thus, standard wide-field imaging methods are still the most common in research laboratories and can often produce measurements with a signal-to-noise ratio that is superior to other optical approaches. This paper seeks to review the most important instrumentation used in these experiments, with particular reference to recent technological advances. We analyse in detail the optical constraints dictating the type of signals that are obtained with voltage and ion imaging and we discuss how to use this information to choose the optimal apparatus. Then, we discuss the available light sources with specific attention to light emitting diodes and solid state lasers. We then address the current state-of-the-art of available charge coupled device, electron multiplying charge coupled device and complementary metal oxide semiconductor cameras and we analyse the characteristics that need to be taken into account for the choice of optimal detector. Finally, we conclude by discussing prospective future developments that are likely to further improve the quality of the signals expanding the capability of the techniques and opening the gate to novel applications. © 2013 Royal Microscopical Society.


Vogt K.E.,University of Basel | Gerharz S.,University of Basel | Graham J.,CAIRN Research Ltd | Canepari M.,French Institute of Health and Medical Research | Canepari M.,Joseph Fourier University
Journal of Physiology | Year: 2011

Combining voltage and Ca 2+ imaging allows the correlation of electrical and chemical activity at sub-cellular level. Here we describe a novel apparatus designed to obtain simultaneous voltage and Ca 2+ measurements with single-trial resolution from sites as small as a few microns. These measurements can be obtained with negligible optical cross-talk between the two signals and negligible photo-damage of the preparation. The capability of the technique was assessed recording either from individual neurons in brain slices or from networks of cultured neurons. The present achievements open the gate to many novel physiological investigations requiring simultaneous measurement of voltage and Ca 2+ signals. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.


Vogt K.E.,University of Basel | Gerharz S.,University of Basel | Graham J.,CAIRN Research Ltd. | Canepari M.,University of Basel | And 2 more authors.
PLoS ONE | Year: 2011

Combining membrane potential imaging using voltage sensitive dyes with photolysis of L-glutamate or GABA allows the monitoring of electrical activity elicited by the neurotransmitter at different sub-cellular sites. Here we describe a simple system and some basic experimental protocols to achieve these measurements. We show how to apply the neurotransmitter and how to vary the dimension of the area of photolysis. We assess the localisation of photolysis and of the recorded membrane potential changes by depolarising the dendrites of cerebellar Purkinje neurons with L-glutamate photorelease using different experimental protocols. We further show in the apical dendrites of CA1 hippocampal pyramidal neurons how L-glutamate photorelease can be used to calibrate fluorescence changes from voltage sensitive dyes in terms of membrane potential changes (in mV) and how GABA photorelease can be used to investigate the phenomenon of shunting inhibition. We also show how GABA photorelease can be used to measure chloride-mediated changes of membrane potential under physiological conditions originating from different regions of a neuron, providing important information on the local intracellular chloride concentrations. The method and the proof of principle reported here open the gateway to a variety of important applications where the advantages of this approach are necessary. © 2011 Vogt et al.


Patent
Cairn Research Ltd | Date: 2014-05-14

There is provided an optical imaging device (10) for splitting an initial image into images with different optical characteristics, wherein the device (10) comprises a plurality of beamsplitters (16, 26, 28) and at least first (20, 20) and second (34, 38, 46, 48) reflective means arranged to create multiple images adjustably separable in two orthogonal directions, characterised in that the first reflective means is rotatable about a first axis (24) and the second reflective means is rotatable about a second axis (56), the second axis (56) orthogonal to the first axis (24). The beamsplitters (16, 26, 28) are located in a first optical layer to create multiple optical pathways directed substantially orthogonally from the first optical layer to a second spaced apart optical layer. Each reflective means (20, 20, 34, 38, 46, 48) can be moved translationally relative to its rotational axis.


Patent
Cairn Research Ltd | Date: 2014-10-14

There is provided an optical arrangement comprising a digital micromirror device having a plurality of individually adjustable mirrors, a mirror pair formed from a convex minor and a concave minor having a common centre of curvature, the concave mirror having a greater radius than the convex mirror, characterised in that a collimated space is immediately adjacent the convex minor, and the concave mirror is offset from the convex mirror so as to be capable of forming an image at an effective focal length of the mirror pair. The convex minor and the concave mirror have radii substantially in the proportion 2.5:1, the concave mirror having the greater radius. A confocal microscope using such an arrangement is also provided.


Patent
Cairn Research Ltd | Date: 2015-05-27

There is provided an optical arrangement comprising a digital micromirror device (62) having a plurality of individually adjustable mirrors, a mirror pair formed from a convex mirror (70) and a concave mirror (72) having a common centre of curvature, the concave mirror (72) having a greater radius than the convex mirror (70), characterised in that a collimated space (76) is immediately adjacent the convex mirror (70), and the concave mirror (72) is offset from the convex mirror (70) so as to be capable of forming an image at an effective focal length of the mirror pair. The convex mirror (70) and the concave mirror (72) have radii substantially in the proportion 2.5:1, the concave mirror having the greater radius. A confocal microscope using such an arrangement is also provided.


Grant
Agency: GTR | Branch: Innovate UK | Program: | Phase: European | Award Amount: 125.59K | Year: 2014

Awaiting Public Project Summary


Patent
Cairn Research Ltd | Date: 2013-11-12

There is provided an optical imaging device for splitting an initial image into images with different optical characteristics, wherein the device comprises a plurality of beamsplitters and at least first and second reflectors arranged to create multiple images adjustably separable in two orthogonal directions, characterised in that the first reflector is rotatable about a first axis and the second reflector is rotatable about a second axis, the second axis orthogonal to the first axis. The beamsplitters are located in a first optical layer to create multiple optical pathways directed substantially orthogonally from the first optical layer to a second spaced apart optical layer. Each reflector can be moved translationally relative to its rotational axis.

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