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Imaging neurotransmitter release to measure synaptic plasticity underlying associative memory

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

Project Description

How does the brain encode memories? We think learning occurs by changes in the strength of synaptic connections between neurons, but the precise mechanisms by which this synaptic plasticity occurs is often unknown. In particular, do changes occur in the pre-synaptic or post-synaptic neuron?

In the fruit fly Drosophila, olfactory associative memories are encoded as changes in synapses from Kenyon cells (which encode odour identity) onto their output neurons (which lead to approach or avoidance behaviour). It is widely believed that these changes occur by reducing pre-synaptic neurotransmitter release from Kenyon cells, but this has never been directly observed, due to technical limitations. Now, thanks to a new genetically-encoded fluorescent sensor for acetylcholine (the neurotransmitter released by Kenyon cells), we are well-placed to overcome these technical limitations.

In this project, the student will carry out the first experimental test of plasticity of pre-synaptic release in this circuit, using a range of cutting-edge techniques, including multiphoton imaging, electrophysiology, fly genetics, 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.

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:
Cognigni, P., Felsenberg, J., & Waddell, S. (2017). Do the right thing: neural network mechanisms of memory formation, expression and update in Drosophila. Current Opinion in Neurobiology, 49, 51–58. http://doi.org/10.1016/j.conb.2017.12.002
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
About the acetylcholine sensor:
Jing, M., Zhang, P., Wang, G., Feng, J., Mesik, L., Zeng, J., et al. (2018). A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nature Biotechnology. http://doi.org/10.1038/nbt.4184

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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