G2C::Electrophysiology::Cultured Neuron

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In the cell electrophysiology team, we use multi-electrode arrays (MEAs) to record the electrical activity of neuronal networks growing on top of a grid of electrodes. On these devices, we grow neurons derived from mice lacking specific synaptic molecules to study how these alterations affect the function of networks of interconnected neurons.

The electrodes detect spontaneous action potentials passing along the neuronal processes as neurons communicate with one another. Because the electrodes are housed within the dish that the neurons are growing in, we can take multiple recordings from the same neurons as they develop in culture. This way, we can monitor how patterns of activity between neurons develop over time.

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By recording from 60 electrodes simultaneously, MEAs allow us to measure the level of activity in a large neuronal network. An increasing number of the electrodes begin to detect increasing numbers of action potentials as the cultures grow older (Valor et al., 2007). MEAs also enable us to detect changes in the pattern of the activity such as the degree of correlation between neurons at disctinct locations on the array. For example, action potentials are more clustered into synchronous bursts in more mature cultures, as illustrated in this quicktime movie

We have multiplexed the equipment used to record from the MEAs to create a platform for high throughput analysis of mouse mutants generated by G2C. Data generated from this project is available in G2Cdb. Alongside these investigations, we can also study the responses of in vitro neuronal networks to a variety of manipulations, such as the application of drugs, small interfering RNAs or electrical stimuli.

Phenotyping Protocols

Protocol Description View
P00000012 Cell electrophysiology of dissociated embryonic hippocampal neurons View

References

  • Network activity-independent coordinated gene expression program for synapse assembly.

    Valor LM, Charlesworth P, Humphreys L, Anderson CN and Grant SG

    Genes to Cognition Programme, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, United Kingdom.

    Global biological datasets generated by genomics, transcriptomics, and proteomics provide new approaches to understanding the relationship between the genome and the synapse. Combined transcriptome analysis and multielectrode recordings of neuronal network activity were used in mouse embryonic primary neuronal cultures to examine synapse formation and activity-dependent gene regulation. Evidence for a coordinated gene expression program for assembly of synapses was observed in the expression of 642 genes encoding postsynaptic and plasticity proteins. This synaptogenesis gene expression program preceded protein expression of synapse markers and onset of spiking activity. Continued expression was followed by maturation of morphology and electrical neuronal networks, which was then followed by the expression of activity-dependent genes. Thus, two distinct sequentially active gene expression programs underlie the genomic programs of synapse function.

    Funded by: Wellcome Trust

    Proceedings of the National Academy of Sciences of the United States of America 2007;104;11;4658-63

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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