Basic NeuroscienceCombined electrophysiological and biosensor approaches to study purinergic regulation of epileptiform activity in cortical tissue

- The purines adenosine and ATP are important endogenous neuroactive compounds.
- They are released during seizures where they influence neuronal activity.
- Enzyme-based biosensors can be used to detect purines in real-time during seizures.
- Sensors can be used with electro/optical techniques to correlate release and activity.
- Together with modelling, new insights in purine release and action can be determined.

BackgroundCortical brain slices offer a readily accessible experimental model of a region of the brain commonly affected by epilepsy. The diversity of recording techniques, seizure-promoting protocols and mutant mouse models provides a rich diversity of avenues of investigation, which is facilitated by the regular arrangement of distinct neuronal populations and afferent fibre pathways, particularly in the hippocampus.New method and resultsWe have been interested in the regulation of seizure activity in hippocampal and neocortical slices by the purines, adenosine and ATP. Via the use of microelectrode biosensors we have been able to measure the release of these important neuroactive compounds simultaneously with on-going epileptiform activity, even of brief durations. In addition, detailed numerical analysis and computational modelling has produced new insights into the kinetics and spatial distribution of elevations in purine concentration that occur during seizure activity.Comparison and conclusionsSuch an approach allows the spatio-temporal characteristics of neurotransmitter/neuromodulator release to be directly correlated with electrophysiological measures of synaptic and seizure activity, and can provide greater insight into the role of purines in epilepsy.

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