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  (MRC DTP) Dense control of neural dynamics by sparse interneuron networks


   Faculty of Biology, Medicine and Health

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  Dr M Humphries, Prof Rasmus Petersen  No more applications being accepted  Competition Funded PhD Project (European/UK Students Only)

About the Project

A wide range of neurological disorders, including Parkinson’s disease, Huntington’s disease and Tourette’s syndrome have been linked to the aberrant activity of output neurons in the massive, subcortical striatum. It is unknown how such aberrant activity arises from the changes to the brain known to occur in these disorders. This project will test the hypothesis that the network of fast-spiking interneurons within the striatum are a common cause of this aberrant activity.

Though they comprise less than one percent of the neuron population, the fast-spiking interneurons are thought to exert powerful control over the striatum’s output. This project will build a full-scale computational model of the fast-spiking interneuron network, and of its control over the striatum’s output neurons. With this model, we will explore how the interneuron network is controlled by its cortical inputs, and how plasticity of the cortical inputs to the network sculpts striatal output during learning. With this understanding in hand, we can then study how changes to that interneuron network result in the pathological dynamics of Parkinson’s disease, and the consequent breakdown of both motor control and cognition.

http://www.systemsneurophysiologylab.manchester.ac.uk/

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website www.manchester.ac.uk/mrcdtpstudentships

Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

References

O'Hare, J. K.; Li, H.; Kim, N.; Gaidis, E.; Ade, K.; Beck, J.; Yin, H. & Calakos, N.
Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual
behavior.
eLife, 2017, 6, e26321
Humphries, M. D.; Wood, R. & Gurney, K.
Reconstructing the three-dimensional GABAergic microcircuit of the striatum
PLoS Computational Biology, 2010, 6, e100101