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The dynamics of single spike-evoked adenosine release\ud in the cerebellum

By Boris P. Klyuch, Magnus J. E. Richardson, Nicholas Dale and Mark J. Wall

Abstract

The purine adenosine is a potent neuromodulator in the brain, with roles in a number\ud of diverse physiological and pathological processes. Modulators such as adenosine are difficult\ud to study as once released they have a diffuse action (which can affect many neurones) and,\ud unlike classical neurotransmitters, have no inotropic receptors. Thus rapid postsynaptic currents\ud (PSCs) mediated by adenosine (equivalent to mPSCs) are not available for study. As a result\ud the mechanisms and properties of adenosine release still remain relatively unclear. We have\ud studied adenosine release evoked by stimulating the parallel fibres in the cerebellum. Using\ud adenosine biosensors combined with deconvolution analysis and mathematical modelling, we\ud have characterised the release dynamics and diffusion of adenosine in unprecedented detail.\ud By partially blocking K+ channels, we were able to release adenosine in response to a single\ud stimulus rather than a train of stimuli. This allowed reliable sub-second release of reproducible\ud quantities of adenosine with stereotypic concentration waveforms that agreed well with predictions\ud of a mathematical model of purine diffusion. We found no evidence for ATP release\ud and thus suggest that adenosine is directly released in response to parallel fibre firing and does\ud not arise from extracellular ATP metabolism. Adenosine release events showed novel short-term\ud dynamics, including facilitated release with paired stimuli at millisecond stimulation intervals\ud but depletion-recovery dynamics with paired stimuli delivered over minute time scales. These\ud results demonstrate rich dynamics for adenosine release that are placed, for the first time, on a\ud quantitative footing and show strong similarity with vesicular exocytosis

Topics: QP
Publisher: Wiley-Blackwell Publishing Ltd.
Year: 2011
OAI identifier: oai:wrap.warwick.ac.uk:4463

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