Investigation of how quantal neurotransmitter release in photoreceptor synapses adapts to changes in input information

Supervisors: Professor Mikko Juusola and Dr Zhuoyi Song

Application deadline: Friday 4 December 2015

Project Description:

Background:

Communication between neurones largely relies upon synaptic information transmission, but little is understood about how this process is regulated by pre- and postsynaptic mechanisms to maximise the flow of information. Information transfer from the photoreceptor output synapses to interneurons is thought to be quantal and continuous, whereupon neurotransmitter is packaged in and released from similarly-sized vesicles. Strikingly, however, our intracellular recordings from the fly eyes in vivo, together with information theoretical metrics and shot-noise analyses now suggest that the sizes of the neurotransmitter (histamine) quanta adapt to the ongoing light conditions. These findings/conclusions are remarkable because they challenge the prevailing “dogma” of synaptic vesicle sizes being uniform and suggest an unexpectedly high degree of adaptability in graded potential synapses.

This project aims to shed important new light to the fundamental pre- and postsynaptic mechanisms, which adapt Drosophila photoreceptors' quantal information transfer for a clearer perception of the world. Importantly, such mechanisms are probably used in the visual systems across the animal kingdom.

Key subject areas: Biophysics, Neuroscience/Neurology

Objectives:

(i) To assess by cryo-EM how the size and numbers of presynaptic vesicles adapt to ongoing stimulation; we shall flash-freeze Drosophila heads in darkness and in different light conditions.
(ii) To compare observations to predictions of stochastic photoreceptor output synapse models.

Novelty: Our preliminary electrophysiological and EM-data implies that synaptic vesicles are larger and more numerous in light than in dark in Drosophila photoreceptors.

Timeliness: These discoveries are highly surprising as the classic view is that synaptic vesicles remain constant and only rates of release would change, but based on our new data both must.

Experimental Approach: Utilise new ultra-fast freezing electron microscopy techniques, Drosophila genetic tools and the state of the art mathematical modelling and analysis to study how photoreceptors' quantal synaptic information transfer adapts to the ongoing light changes.

Funding:

Competition-funded project (Students worldwide)

References:

  • Song, Z. & Juusola, M. (2014). Refractory Sampling Links Efficiency and Costs of Sensory Encoding to Stimulus Statistics. J. Neurosci. 34: 34: 7216 –7237.
  • Juusola, M., Song, Z. & Hardie, R.C. (2015). Phototransduction Biophysics. Encyclopedia of Computational Neuroscience (Springer Verlag), pp 2359-2376.
  • Wardill, T., List, O., Li, X., Dongre, S., MCCulloch, M., Ting, C.-Y., O’Kane. C.J., Tang, S., Lee, C.-H., Hardie, R.C. & Juusola, M. (2012). Multiple spectral inputs contribute to motion discrimination in the Drosophila visual system. Science 336: 925-931.
  • Song, Z., Postma, M., Billings, S.A., Coca, D., Hardie, R.C. & Juusola, M. (2012). Stochastic, Adaptive Sampling of Information by Microvilli in Fly photoreceptors. Curr. Biol. 22: 1-10.

Contact details

Professor Mikko Juusola

Web: https://www.shef.ac.uk/bms/research/juusola

Email: M.Juusola@sheffield.ac.uk

Further Information:

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