Exploring novel multi-modal photonic techniques for live imaging of synaptic activity

Overview

The importance of learning and memory in determining who we are is made starkly obvious in patients with late-stage dementia. Developing therapies to treat dementia therefore requires a fundamental understanding of learning at the molecular level. When we learn, information is encoded in our brains by the strengthening of connections (synapses) between brain cells (neurons). The expertise of a neuroscientist and a physicist have been paired in this project to develop a novel method for measuring the activity of synapses in neurons that will facilitate basic research into how synapses change when we learn.

A microscope that uses changes in the properties of light to detect the binding of neurotransmitters to specific sensors will be constructed to observe the chemical neurotransmitters that are released by active synapses during the course of learning. This novel technique will reveal how networks of synapses behave and so help to elucidate the molecular processes of learning, and how these processes go wrong in dementia.

In detail

The importance of learning and memory in determining who we are is made starkly obvious in patients with late-stage dementia. Developing therapies to treat dementia therefore requires a fundamental understanding of learning at the molecular level. When we learn, information is encoded in our brains by the strengthening of connections (synapses) between brain cells (neurons). The expertise of a neuroscientist and a physicist will be paired to develop a novel method for measuring the activity of synapses in neurons that will facilitate basic research into how synapses change when we learn.

A novel microscope has been designed and constructed that exploits changes in the properties of light to observe the chemical neurotransmitters that are released by active synapses during the course of learning. This microscope can visualise cellular fluorescence and detect cell features due to fluctuations in refractive index. This novel technique will help to reveal how networks of synapses behave and hence to elucidate the molecular processes of learning and how these processes go wrong in dementia.

Considerable effort has been spent on optimising the design and fabrication of silicon crystals that resonate and can detect changes in refractive index as a rusult of cellular processes as well as on optimising the culture of neuronal cells on photonic crystals. Using a simpler 'ring' resonator, we have also successfully detected antibody-antigen interactions on a crystal surface.

Thus the components of the proposed system to measure neurotransmitter release have been developed independently and collaborative work between the Krauss and Evans labs will continue to combine these technologies to image neurotransmission and synaptic plasticity label-free and in real time.

The project has also stimulated discussions between the Krauss lab and other biologists to develop specific biosensors.  A collaboration was hence formed between the Krauss lab and Mark Coles (HYMS, CII) for detecting chemokines.

Outputs

Grants

• Thomas Krauss, BBSRC, Label-free, Real-time, Spatial-resolution (LRS) immunoassay: 2D mapping of extracellular signalling molecules, £181,954.14