Abstract
Endocannabinoids (eCBs) modulate both excitatory and inhibitory neurotransmission in hippocampus via activation of pre-synaptic cannabinoid receptors. Here, we present a model for cannabinoid mediated short-term depression of excitation (DSE) based on our recently developed model for the equivalent phenomenon of suppressing inhibition (DSI). Furthermore, we derive a simplified formulation of the calcium-mediated endocannabinoid synthesis that underlies short-term modulation of neurotransmission in hippocampus. The simplified model describes cannabinoid-mediated short-term modulation of both hippocampal inhibition and excitation and is ideally suited for large network studies. Moreover, the implementation of the simplified DSI/DSE model provides predictions on how both phenomena are modulated by the magnitude of the pre-synaptic cell’s activity. In addition we demonstrate the role of DSE in shaping the post-synaptic cell’s firing behaviour qualitatively and quantitatively in dependence on eCB availability and the pre-synaptic cell’s activity. Finally, we explore under which conditions the combination of DSI and DSE can temporarily shift the fine balance between excitation and inhibition. This highlights a mechanism by which eCBs might act in a neuro-protective manner during high neural activity.






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Acknowledgements
The authors would like to thank Chris Christodoulou and Stephen Coombes for useful comments and discussions. The authors also wish to acknowledge the anonymous reviewers for their helpful comments to the manuscript. This work was co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research Promotion Foundation (DIDAKTOR/0609/12) and by a Young Researchers grant from the University of Cyprus.
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Zachariou, M., Thul, R. Cannabinoid-mediated short-term plasticity in hippocampus. J Comput Neurosci 37, 533–547 (2014). https://doi.org/10.1007/s10827-014-0518-4
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DOI: https://doi.org/10.1007/s10827-014-0518-4