Multiplexed Super-Resolution Single Molecule FISH: Role of Glial mRNA Localisation in Synaptic Plasticity

On Demand

Professor Ilan Davis

MVLS chair of Spatial Biomedicine, University of Glasgow

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Recorded live from Imperial College London.

In neurones, the translation of localised mRNAs is thought to underpin synaptic plasticity by enabling rapid and distinct responses in different distal synapses. Glia have recently emerged as similar to neurones in structure and importance for nervous system function. Glial cells, like neurones, have long cytoplasmic projections that contact many other glial cells and multiple different neurones. These projections are known to regulate the plasticity of synapses they contact, which are now thought of as tri-partite, consisting of dendritic, axonal and glial projections. However, the mechanisms of such regulation are still poorly understood, as is the role of localised translation in glia. In this video, Professor Ilan Davis presents his group’s emerging evidence to supports the hypothesis that localised translation of glial mRNAs encoding a wide range of cellular functions in distal cytoplasmic projections are essential for the plasticity of their adjacent neuronal synapses. They have already discovered 1700 transcripts, enriched in neurological disease associations, that are predicted to localise at distal glial cytoplasmic projections. Using single molecule FISH (smFISH) has shown experimentally an enrichment in glial localised transcripts. Some of the mRNAs are specifically required in the glia, not the neurones, for forming normal actin-rich cytoplasmic projections, neuronal plasticity in adjacent synapses and correct larval crawling behaviour. This work expands the known frontier of localised mRNA in distal glial projections, their interactions with neurones and mechanisms and function in neuronal plasticity. Professor Davis also discusses the implications of their data for the regulation of distal cellular functions by localised translation in other cellular contexts, as well as potential novel mechanistic explanations of diseases of the nervous system. In the second half of the talk, he explores the prospects for increasing the coverage of detection of many transcripts at high plex, making use of modern confocal instruments with spectral separation and super-resolution. He describes his group’s own efforts to develop approaches that democratise spatial biology and their aspirations in the context of the current landscape of commercial spatial biology approaches.

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