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  • Dendritic Integration of Sensory Evidence in Perceptual Decision-Making.

    3 July 2018

    Perceptual decisions require the accumulation of sensory information to a response criterion. Most accounts of how the brain performs this process of temporal integration have focused on evolving patterns of spiking activity. We report that subthreshold changes in membrane voltage can represent accumulating evidence before a choice. αβ core Kenyon cells (αβc KCs) in the mushroom bodies of fruit flies integrate odor-evoked synaptic inputs to action potential threshold at timescales matching the speed of olfactory discrimination. The forkhead box P transcription factor (FoxP) sets neuronal integration and behavioral decision times by controlling the abundance of the voltage-gated potassium channel Shal (KV4) in αβc KC dendrites. αβc KCs thus tailor, through a particular constellation of biophysical properties, the generic process of synaptic integration to the demands of sequential sampling.

  • Aberrations in stimulated emission depletion (STED) microscopy.

    3 July 2018

    Like all methods of super-resolution microscopy, stimulated emission depletion (STED) microscopy can suffer from the effects of aberrations. The most important aspect of a STED microscope is that the depletion focus maintains a minimum, ideally zero, intensity point that is surrounded by a region of higher intensity. It follows that aberrations that cause a non-zero value of this minimum intensity are the most detrimental, as they inhibit fluorescence emission even at the centre of the depletion focus. We present analysis that elucidates the nature of these effects in terms of the different polarisation components at the focus for two-dimensional and three-dimensional STED resolution enhancement. It is found that only certain low-order aberration modes can affect the minimum intensity at the Gaussian focus. This has important consequences for the design of adaptive optics aberration correction systems.

  • Snapshot coherence-gated direct wavefront sensing for multi-photon microscopy.

    2 July 2018

    Deep imaging in turbid media such as biological tissue is challenging due to scattering and optical aberrations. Adaptive optics has the potential to compensate the tissue aberrations. We present a wavefront sensing scheme for multi-photon scanning microscopes using the pulsed, near-infrared light reflected back from the sample utilising coherence gating and a confocal pinhole to isolate the light from a layer of interest. By interfering the back-reflected light with a tilted reference beam, we create a fringe pattern with a known spatial carrier frequency in an image of the back-aperture plane of the microscope objective. The wavefront aberrations distort this fringe pattern and thereby imprint themselves at the carrier frequency, which allows us to separate the aberrations in the Fourier domain from low spatial frequency noise. A Fourier analysis of the modulated fringes combined with a virtual Shack-Hartmann sensor for smoothing yields a modal representation of the wavefront suitable for correction. We show results with this method correcting both DM-induced and sample-induced aberrations in rat tail collagen fibres as well as a Hoechst-stained MCF-7 spheroid of cancer cells.

  • Data driven identification and aberration correction for model based sensorless adaptive optics

    2 July 2018

    Wavefront sensorless adaptive optics methodologies are considered in many applications where the deployment of a dedicated wavefront sensor is inconvenient, such as in fluorescence microscopy. In these methodologies, aberration correction is achieved by sequentially changing the settings of the adaptive optical element until a predetermined imaging quality metric is optimised. Reducing the time required for this optimisation is a challenge. In this paper, a two stage data driven optimisation procedure is presented and validated in a laboratory environment. In the first stage, known aberrations are introduced by a deformable mirror and the corresponding intensities are measured by a photodiode masked by a pinhole. A generic quadratic metric is fitted to this collection of aberrations and intensity measurements. In the second stage, this quadratic metric is used in order to estimate and correct for optical aberrations. A closed form expression for the optimisation of the quadratic metric is derived by solving a linear system of equations. This requires a minimum of N +1 pairs of deformable mirror settings and intensity measurements, where N is the number of modes of the aberrations. © 2012 SPIE.

  • Focal-plane wavefront estimation and control using the extended Kalman filter

    2 July 2018

    This paper addresses the problem of disturbance rejection for faint Poisson point-like measurements. The aberration function is approximated with a finite Zernike based expansion. We use nonlinear observers to estimate the aberrations and a linear quadratic regulator to reject the aberrations. Kalman filtering is compared with the phase diversity maximum aposteriori estimation. The approach presented here is beneficial for instance for 2-photon observations, single molecule observations or natural/laser guide star observations in astronomy. © 2012 IEEE.

  • Semidefinite programming for model-based sensorless adaptive optics.

    2 July 2018

    Wavefront sensorless adaptive optics methodologies are widely considered in scanning fluorescence microscopy where direct wavefront sensing is challenging. In these methodologies, aberration correction is performed by sequentially changing the settings of the adaptive element until a predetermined image quality metric is optimized. An efficient aberration correction can be achieved by modeling the image quality metric with a quadratic polynomial. We propose a new method to compute the parameters of the polynomial from experimental data. This method guarantees that the quadratic form in the polynomial is semidefinite, resulting in a more robust computation of the parameters with respect to existing methods. In addition, we propose an algorithm to perform aberration correction requiring a minimum of N+1 measurements, where N is the number of considered aberration modes. This algorithm is based on a closed-form expression for the exact optimization of the quadratic polynomial. Our arguments are corroborated by experimental validation in a laboratory environment.

  • Modal-based phase retrieval for adaptive optics.

    2 July 2018

    We consider using phase retrieval (PR) to correct phase aberrations in an optical system. Three measurements of the point-spread function (PSF) are collected to estimate an aberration. For each measurement, a different defocus aberration is applied with a deformable mirror (DM). Once the aberration is estimated using a PR algorithm, we apply the aberration correction with the DM, and measure the residual aberration using a Shack-Hartmann wavefront sensor. The extended Nijboer-Zernike theory is used for modelling the PSF. The PR problem is solved using both an algorithm called PhaseLift, which is based on matrix rank minimization, and another algorithm based on alternating projections. For comparison, we include the results achieved using a classical PR algorithm, which is based on alternating projections and uses the fast Fourier transform.

  • Domingos

    12 July 2018

    We investigate neuroimmune molecular mechanisms underlying obesity.

  • Vogels Group

    10 July 2016

    Theoretical and Computational Neuroscience

  • Vyazovskiy Group

    16 December 2013

    Sleep, brain and behaviour laboratory

  • Davies Group

    10 July 2016

    Molecular Analysis of Neurological Disorders

  • Herring Group

    22 January 2015

    Local neuromodulators of cardiac autonomic control

  • Ma Group

    19 January 2016

    The aim of our work is to determine the cellular mechanisms underlying the benefits of traditional multi-herbal Chinese medicines.

  • Threlfell Group

    8 April 2014

    Exploring mechanisms underlying dopamine neuron vulnerability in Parkinson's disease

  • Cantley Group

    10 July 2016

    Beta cell function, obesity and type 2 diabetes

  • Mommersteeg Group

    3 July 2014

    Heart regeneration & development

  • Molnar Group

    10 July 2016

    Cerebral Cortical Development and Evolution

  • Metabolism & Endocrinology

    16 January 2018

    We use the full range of modern molecular genetic and imaging techniques to study a range of metabolic areas.

  • Cardiac Sciences

    26 April 2018

    We are recognised internationally for our pioneering approaches to systems biology and to computational modelling of the heart.

  • Functional Genomics

    16 January 2018

    We play a leading role in the development of more efficient and cost-effective sequencing technologies.

  • Neuroscience

    16 January 2018

    We host a number of internationally recognised neuroscience groups, with expertise in a wide range of experimental and computational methods.

  • Cell Physiology

    16 January 2018

    We study everything from the structure of ion channels and transporters right up to their role in behaviour and human disease.

  • Development & Cell Biology

    16 January 2018

    We dissect the molecular and cellular mechanisms underlying a range of developmental and reproductive processes.