Dr Andrew Lin

Andrew Lin

Vice-Chancellor's Fellow
Department of Biomedical Science
University of Sheffield
Western Bank
Sheffield S10 2TN
United Kingdom

Room: B2 228 Alfred Denny building
Telephone: +44 (0) 114 222 3643
Email: andrew.lin@sheffield.ac.uk

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Centre for Sensory Neuroscience
General

Brief career history

  • 2015 - present: Vice-Chancellor’s Fellow, University of Sheffield
  • 2009 - 2015: Postdoctoral fellow, University of Oxford. Advisor: Gero Miesenböck
  • 2004 - 2009: PhD, University of Cambridge. Advisor: Christine Holt
  • 2000 - 2004: AB Biology, Harvard University

Research interests

We study how the brain represents sensory information to allow it to store unique memories, using the olfactory system of the fruit fly Drosophila melanogaster as a model system.


Full Publications

Research

Olfactory sensory coding and memory

How does the brain recognise sensory stimuli? How does it form distinct memories for different stimuli, even very similar ones? And how does it wire itself up to process information in the best way to achieve these remarkable feats? Our research addresses these fundamental questions using the olfactory system of the fruit fly Drosophila melanogaster. Flies have a much simpler nervous system than humans but are still capable of complex behaviours such as associative memory. This simplicity, combined with the power of fly genetics, makes Drosophila an excellent model system for tackling basic questions about neural circuit function.

Flies can form distinct associative memories for different odours, even very similar ones, and this stimulus-specificity depends on ‘sparse coding’, in which Kenyon cells, the neurons that encode olfactory associative memories, respond sparsely to odours, i.e. only a few neurons in the population respond to each odour. This sparse coding in turn depends on a delicate balance of excitation and inhibition onto Kenyon cells. We are studying how this balance is created and maintained. By improving our understanding of how the brain balances excitation and inhibition, this work may shed light on neurological disorders, like epilepsy, where this balance goes wrong.

Some methods we use:

  • In vivo two-photon imaging
  • Patch-clamp electrophysiology
  • Individual-fly behavioural experiments
  • Genetic manipulation of identified neurons
  • Transcriptional profiling
  • Computational modelling
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS349 Extended Library Project
  • BMS355 Sensory Neuroscience
Opportunities

Postgraduate studentship opportunities

1. Cellular mechanisms underlying homeostatic balancing of neuronal excitation and inhibition in vivo

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 insufficient inhibition onto Kenyon cells, excitatory synapses onto Kenyon cells might become weaker or smaller, or Kenyon cells might decrease their input resistance to become intrinsically less 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.

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, 559-68.
  • Review about homeostatic plasticity: Davis, G. W. (2013). Homeostatic signaling and the stabilization of neural function. Neuron 80, 718–728.

For informal enquiries about this project, please contact:

To find out more about these projects and how to apply see our PhD opportunities page:

PhD Opportunities

Selected publications

Journal articles