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MBPhD Programme

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BROWN, Alexander Philip Yehuda

Entered:

July 2010

Current Position: 

Graduated 2017

PhD title: 

Intrinsic and Visually-Evoked Properties of Layer 2/3 Neurons in Mouse Primary Visual Cortex and Their Dependence on Sensory Experience

Principal Supervisor: 

Prof Troy Margrie, Sainsbury Wellcome Centre (UCL)

Funding Source: 

National Institute for Medical Research

Summary:

Neurons in primary visual cortex (V1) are known to respond strongly to visual stimuli. Studies of neuronal responses in V1, carried out first in cats, but later primates and other mammals, have demonstrated that bars of light at particular orientations evoke strong, reliable responses in terms of increased firing rate of action potentials. Tuning of neuronal responses to certain stimulus parameters, such as orientation but also spatial and temporal frequencies, as well as the apparent dichotomy between simple and complex responses, have given rise to a number of influential models not just of V1 function, but more generally in the field of cortical physiology and computer vision.

Owing to its small size and the plethora of available molecular and genetic tools, the visual cortex of the mouse may be a more tractable model system than that of much larger animals. Recent studies of neuronal responses in mouse V1 have shown that these are broadly similar to those of primates and carnivores, although not identical in all aspects.

My project aimed firstly to characterise intrinsic and sensory-evoked properties in regular- spiking, putative pyramidal neurons in the upper layers of the mouse visual cortex using whole-cell patch clamp recording in vivo . We found that, in the mouse, the overwhelming majority of these neurons are simple cells. Orientation tuning (the degree to which neuronal responses are selective to stimuli of a preferred orientation) was quite variable, even within this singular group of neurons.

In addition, I used virus-assisted circuit mapping to characterise the anatomical connectivity of individual neurons and groups of neurons from identified molecular classes, in order to address the question of whether diverse functional responses arise from heterogeneity in functional connectivity or intrinsic properties of the individual cell. This work is still ongoing.

These findings provide an insight in to how diverse responses to sensory stimuli can be generated in an apparently homogenous group of neurons – how a slab of uniform brain tissue can create the rich visual scenes we see every time we open our eyes.

Publications:

Brown, APY & Greenberg, HZ What they don’t teach you in medical school: Patch Clamp. British Journal of Hospital Medicine (In Press).

Vélez-Fort, M, Rousseau, CV, Niedworok, CJ, Wickersham, IR, Rancz, EA, Brown, APY, Strom M, Margrie, TW (2014). The Stimulus Selectivity and Connectivity of Layer Six Principal Cells Reveals Cortical Microcircuits Underlying Visual Processing. Neuron, 1431–1443. doi:10.1016/j.neuron.2014.08.001

Brown, APY, Margrie, TW (2012). Calcium Imaging with Recovery: a novel method for studying neuronal function. Poster Presentation, European MB/PhD Conference, University College London.

Teaching:

2012-2013: Postgraduate Teaching Assistant (Anatomy Demonstrator) Dept. of Cell and Developmental Biology, University College London

2011, 2012: ‘The Doctor as a scholar and scientist’ University College London

Awards & Prizes:

2014: MedTech Hackathon (Team Observant, Runner-up)

2013: MRC Centenary Fellowship

2012:  Poster Prize (awarded by the Journal of Pathology), European MB PhD Conference