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New Sensor Discovery Has Implications for Brain Research

Summary: Researchers have developed an ultra fast sensor that binds to glutamate. The sensor, dubbed iGluu, is being made available to other researchers to further their neuroscience studies.

Source: St. George’s University of London

An ultrafast sensor which binds to glutamate will allow scientists to visualise messaging at the synapses – which occurs on a millisecond timescale.

Nerve cells communicate through synapses, which pass messages from one neuron to another via small molecules such as glutamate. Although sensors have previously been developed to help scientists see this signalling, it occurs so extremely fast that even the best sensors have been unable to accurately track the process until now.

The sensor, iGluu, will now be made available to other researchers who may be working on either the fundamental properties of neuronal signalling or on neurodegenerative disease such as Huntington’ and Alzheimer’s disease. The sensor will help reveal what goes wrong with glutamate signalling in these conditions.

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Nerve cells communicate through synapses, which pass messages from one neuron to another via small molecules such as glutamate. NeuroscienceNews.com image is adapted from the St. George’s University London news release.

Katalin Török, Reader in Cell Biology at St George’s, University of London, said: “This sensor has helped us to answer long-standing questions about the complex molecular mechanisms that occur during neuronal signalling. We can now directly demonstrate that neurotransmitter glutamate is rapidly cleared from the synapse. We now have a sensor to look at synapses in more detail than ever before, this will allow researchers to test theories about how the brain functions.”

About this neuroscience research article

Source: St. George’s University of London
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the St. George’s University London news release.
Original Research: Open access research for “Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses” by Nordine Helassa, Céline D. Dürst, Catherine Coates, Silke Kerruth, Urwa Arif, Christian Schulze, J. Simon Wiegert, Michael Geeves, Thomas G. Oertner, and Katalin Török in PNAS. Published May 7 2018.
doi:10.1073/pnas.1720648115

Cite This NeuroscienceNews.com Article
St. George’s University of London “New Sensor Discovery Has Implications for Brain Research.” NeuroscienceNews. NeuroscienceNews, 17 May 2018.
<http://neurosciencenews.com/glutamate-sensor-9079/>.
St. George’s University of London (2018, May 17). New Sensor Discovery Has Implications for Brain Research. NeuroscienceNews. Retrieved May 17, 2018 from http://neurosciencenews.com/glutamate-sensor-9079/
St. George’s University of London “New Sensor Discovery Has Implications for Brain Research.” http://neurosciencenews.com/glutamate-sensor-9079/ (accessed May 17, 2018).

Abstract


Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses

Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGluf) and ultrafast (iGluu) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGluu has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGluu is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGluu responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.

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