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Homeostatic balancing of neuronal excitation and inhibition in vivo

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Neuronal excitation and inhibition are very carefully balanced in the brain, and perturbed excitation/inhibition (E/I) balance has been linked to diseases such as epilepsy, autism and schizophrenia. Maintaining E/I balance within normal bounds depends in part on homeostatic plasticity, in which neurons compensate for deviations in activity levels by adjusting their responsiveness to excitation and inhibition. Although we are starting to understand the molecular mechanisms underlying homeostatic plasticity in reduced preparations, we still know very little about such mechanisms in the intact brain.

We have recently developed a new model system for addressing this question. In the fruit fly Drosophila, Kenyon cells (KCs), the neurons underlying olfactory associative memory, receive excitation from projection neurons as well as feedback inhibition from a single identified neuron. The balance between these two forces maintains sparse odour coding in Kenyon cells, which enhances the odour-specificity of associative memory by reducing overlap between odour representations. Preliminary evidence indicates that Kenyon cells adapt to prolonged disruption of E/I balance, providing a unique opportunity to use the powerful genetic tools of Drosophila to uncover the molecular mechanisms underlying homeostatic plasticity in the intact brain, in a defined circuit that mediates a sophisticated behaviour.

This project will test candidate cellular mechanisms underlying homeostatic compensation. For example, to compensate for excess inhibition onto Kenyon cells, excitatory synapses onto Kenyon cells might become bigger or stronger, or Kenyon cells might increase their input resistance to become intrinsically more excitable. In testing whether these or other mechanisms underlie homeostatic plasticity in vivo, the student will develop skills in a wide range of techniques from fly genetics and confocal microscopy to patch-clamp electrophysiology, two-photon imaging of neural activity, and computational modelling.

Science Graduate School
As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.
https://www.sheffield.ac.uk/bms/study/prospective_pg

Funding Notes

Entry requirements
First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

*All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information*.

References

References:
About the model system:
Lin, A. C., Bygrave, A. M., de Calignon, A., Lee, T., & Miesenböck, G. (2014). Sparse, decorrelated odor coding in the mushroom body enhances learned odor discrimination. Nature Neuroscience, 17(4), 559–568. http://doi.org/10.1038/nn.3660
Review about homeostatic plasticity:
Davis, G. W. (2013). Homeostatic signaling and the stabilization of neural function. Neuron, 80(3), 718–728. http://doi.org/10.1016/j.neuron.2013.09.044

web: http://www.sheffield.ac.uk/bms/research/lin
http://www.aclinlab.org
email: [email protected]

How good is research at University of Sheffield in Biological Sciences?

FTE Category A staff submitted: 44.90

Research output data provided by the Research Excellence Framework (REF)

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