Multicellular recording system to investigate central nervous system dynamics

Lead Research Organisation: Newcastle University
Department Name: Neurology Neurobiology and Psychiatry

Abstract

In the brain, specific neural activity patterns arise from the simultaneous activation of thousands or millions of neurones interconnected in a very specific way, conveying unique properties to the entire network. Therefore, if we want to investigate how neurones communicate with each other, we need to record from many cells simultaneously. Thanks to new technologies, this is now possible. Impulses generated by neurones can be recorded with electrodes that detect electrical activity. Large arrays of many of these electrodes are now available, enabling us to record simultaneously from dozens of sites. Optical recordings, on the other hand, allow us to visualise changes in the concentration of various ions that are involved in the control of neural activity, while they are flowing across the membrane of the active neurones. These ionic fluxes can be linked either to neural excitation or inhibition and are therefore not necessarily reflecting impulse generation. Taken together, the combination of electrical and optical recordings over large-scale neuronal networks provides a powerful tool to help us understand the mechanisms of neuronal communication in much greater detail. In this proposal, we intend to establish a state-of-the-art system that will allow us to perform electrical recordings from a 60-electrode array at the same time as high resolution imaging of neuronal activity. The system will be used for several projects, ranging from investigating the behaviour of embryonic retinal networks to the generation and control of cortical and hippocampal oscillations associated with various cognitive states. Moreover, it will also represent an invaluable experimental tool to help in the design of a device that has the huge potential to become the platform for the development of a retinal implant that could help restore impaired visual perception following retinal dystrophic diseases.

Technical Summary

To elucidate communication within specific networks, we must investigate both subthreshold synaptic activity (excitation and inhibition) and suprathreshold spiking activity. Recent advances in electrode technology and cellular imaging (including animal models expressing ion-sensitive fluorescent probes) now give us the tremendous opportunity to combine all these approaches into one experimental set-up to investigate the properties of neural networks with high spatial and temporal resolution. Subthreshold signals can be deciphered by multicellular imaging of neurotransmitter-driven modification in various ionic conductances and concentrations. At the same time, concurrent recording from many spiking neurones is possible using multielectrode arrays. The basis of this application is to establish a state-of-the-art MultiElectrode Recording and Imaging Station (MERIS) that will be used in a range of projects in which the outcomes are either reliant on, or greatly facilitated by these technologies. Moreover, multicellular recording has the great advantage of reducing the number of experiments required to obtain significant data. The projects in this proposal range from investigating wave dynamics in the developing retina to dynamic network behaviour in the neocortex and in the hippocampus. In addition, the MERIS will be used in a project aimed at developing high density multielectrode arrays that will be used to design retinal prostheses.

Publications

10 25 50
 
Description This equipment is continuously being used for various projects investigating the behaviour of small neural networks, allowing us to record electrical activity from a population of neurones while being able to visualise them as well.
Exploitation Route combining electrical and optical recordings is becoming increasingly common in neuroscience research
Sectors Education

Healthcare

Pharmaceuticals and Medical Biotechnology

 
Description This equipment grant allowed us to purchase a system allowing us to perform multielectrode array recordings together with calcium imaging
First Year Of Impact 2008
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal

 
Description MICA: An iPSC based screen for candidate pain modulating compounds
Amount £571,447 (GBP)
Funding ID MR/R011338/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2018 
End 03/2021
 
Title retinal waves data repository Gigascience 
Description database of retinal wave recordings from our laboratory, stored on the CARMEN repository for public sharing 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact Several computational scientists have accessed the data and used in their models/simulations