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EASTBIO: Towards a systems-level understanding of visually-guided reaching


Project Description

Deanery of Biomedical Sciences
Reaching and grasping is an essential component of our everyday lives. We use visual information regarding object type and position and combine this with exquisite and adaptable motor control to successfully interact with objects in our environment. This process is thought to involve brain areas concerned with visual perception (primary visual & posterior parietal cortices) and action selection (basal ganglia), which converge at the level of the frontal motor cortex to select the correct action type and execute / update reaching movements. Although we have an in-depth understanding of the brain areas involved, the cellular and circuit computations underpinning visually-guided reaching and updating remain unresolved. In this programme of work, we will test three main hypotheses:


Hypotheses:

1) The primary visual cortex and posterior parietal cortex drive visual responses in frontal motor cortex during visually-guided reaching.

2) The basal ganglia-thalamocortical pathway conveys action type-specific information to frontal motor regions.

3) Frontal motor regions act as a visuomotor convergence hub necessary for executing visually-guided reaching.


To test these hypotheses, we will use a multidisciplinary approach combining large-scale 2-photon population calcium imaging of neural activity, in vivo electrophysiology, viral based manipulation strategies, 3D kinematic analysis of movement, quantitative behaviour and Bayesian decoders of population data. This project will be conducted in collaboration with Dr Matthias Hennig (School of Informatics, University of Edinburgh), Dr. Aldo Faisal (Dept. of Bioengineering, Imperial College London) and Dr Marcus Stephenson-Jones (Sainsbury Wellcome Centre for Neural Circuits & Behaviour, UCL) and will address 3 main aims:

Aim 1: Develop and optimise a novel dual-target visually-guided reaching task for mice. To investigate the neural underpinnings of visually-guided reaching in mice we will implement and optimise a cued 2-choice visually-guided reaching task in mice that can be adapted to update the visual target upon reach initiation. This provides a task where both visually-guided reaching and online movement updating can be investigated.

Aim 2: Determine the population-level representations of visually-guided reaching in frontal and subcortical motor regions. We will use wide-field 2-photon population calcium imaging and electrophysiological recordings of neuronal activity in frontal and subcortical motor regions (basal ganglia / motor thalamus) during execution of a visually-guided reaching task and during movement updating trials. Viral-based opto-/chemogenetic manipulation strategies will be used to investigate causality between the activity of visual and motor projections to frontal motor areas.

Aim 3: Use dimensionality reduction methods and Bayesian decoders to explore causal links between neuronal activity patterns in frontal motor regions and online forelimb kinematics. Using population imaging and electrophysiology data generated in Aims 1 & 2, we will use dimensionality reduction methods and will build Brain Machine Interface (BMI) decoders to predict limb trajectories from neuronal population activity. By applying advanced computational methods and computer vision algorithms we will develop an in-depth understanding of how single cell and network dynamics in frontal motor regions combine to generate accurate, visually-guided reaches and online movement updating.

Training outcomes
This project will provide the student with practical skills in experimental design, 2-photon imaging, in vivo electrophysiology, statistics and advanced computational methods for data analysis. The student will benefit from experimental, computational and theoretical input from some of the leading experimentalists and computational neuroscientists in the UK. This will be achieved by short trips to Imperial College and Sainsubury Wellcome Centre for Neural Circuits and Behaviour at UCL to directly work will our collaborators.

References:
C Bosch-Bouju, B Hyland, and L Parr-Brownlie. Motor thalamus integration of cortical, cerebellar
and basal ganglia information: implications for normal and parkinsonian conditions. Frontiers in
Computational Neuroscience, 7, 2013.

N Li, T Chen, Z Guo, C Gerfen, and K Svoboda. A motor cortex circuit for motor planning and
movement. Nature, 519(7541), 2015. ISSN 0028-0836.

M A Umilta, T Brochier, R L Spinks, and R N Lemon. Simultaneous recording of macaque premotor
and primary motor cortex neuronal populations reveals different functional contributions to
visuomotor grasp. Journal of neurophysiology, 98(1), 2007.

Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership. This opportunity is only open to UK nationals (or EU students who have been resident in the UK for 3+ years immediately prior to the programme start date) due to restrictions imposed by the funding body. EU applicants without a history of residency in the UK are eligible to apply, but would only be awarded the fees (not the stipend). All candidates should have or expect to have a minimum of an upper 2nd class degree in an appropriate discipline.

References

Download application and reference forms via: http://www.eastscotbiodtp.ac.uk/how-apply-0
Completed application form along with your supporting documents should be sent to our PGR student team at [email protected] by 5th January 2020.

References: Please send the reference request form to two referees. Completed references for this project should also be returned to [email protected] by the closing date: 5th January 2020.

It is your responsibility to ensure that references are provided by the specified deadline.

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