Multicellular recording system to investigate central nervous system dynamics

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.

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.