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The Journal of Neuroscience, May 17, 2006, 26(20):5428-5437; doi:10.1523/JNEUROSCI.5284-05.2006

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Cellular/Molecular
Dendritic Calcium Spikes Are Tunable Triggers of Cannabinoid Release and Short-Term Synaptic Plasticity in Cerebellar Purkinje Neurons

Ede A. Rancz and Michael Häusser

Wolfson Institute for Biomedical Research and Department of Physiology, University College London, London WC1E 6BT, United Kingdom

Correspondence should be addressed to Michael Häusser, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom. Email: m.hausser{at}ucl.ac.uk

Understanding the relationship between dendritic excitability and synaptic plasticity is vital for determining how dendrites regulate the input–output function of the neuron. Dendritic calcium spikes have been associated with the induction of long-term changes in synaptic efficacy. Here we use direct recordings from cerebellar Purkinje cell dendrites to show that synaptically activated local dendritic calcium spikes are potent triggers of cannabinoid release, producing a profound and short-term reduction in synaptic efficacy at parallel fiber synapses. Enhancing dendritic excitability by modulating dendritic large-conductance calcium-activated potassium (BK) channels improves the spread of dendritic calcium spikes and enhances cannabinoid release at the expense of spatial specificity. Our findings reveal that dendritic calcium spikes provide a local and tunable coincidence detection mechanism that readjusts synaptic gain when synchronous activity reaches a threshold, and they reveal a tight link between the regulation of dendritic excitability and the induction of synaptic plasticity.

Key words: dendritic spike; endocannabinoid; BK channel; DSE; Purkinje cell; cerebellum

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Received Dec. 11, 2005; revised April 10, 2006; accepted April 10, 2006.

Correspondence should be addressed to Michael Häusser, Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, United Kingdom. Email: m.hausser{at}ucl.ac.uk

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