On Oct 21, 2009, the Journal of Neuroscience published a full research article from ION entitled "Endocannabinoid-Dependent Homeostatic Regulation of Inhibitory Synapses by Miniature Excitatory Synaptic Activities”. This work was carried out by graduate students Si-yu Zhang, Min Xu and Qing-long Miao, as a collaboration between the laboratories of Drs. Xiao-hui Zhang and Mu-ming Poo at ION. 

Homeostatic regulation of synaptic strength in response to persistent changes of neuronal activity plays an important role in maintaining the overall level of circuit activity within a normal range. Absence of miniature excitatory postsynaptic currents (mEPSCs) for a few hours is known to cause up-regulation of excitatory synaptic strength, suggesting that mEPSCs contribute to the maintenance of excitatory synaptic functions. Their study shows that the absence of mEPSCs for 1–3 h also results in homeostatic suppression of presynaptic functions of inhibitory synapses in acute cortical slices from juvenile rats, as suggested by the reduced frequency (but not amplitude) of miniature inhibitory postsynaptic currents (mIPSCs) as well as the reduced amplitude of IPSCs. This homeostatic regulation requires the activation of endocannabinoid (eCB) signaling and group I metabotropic glutamate receptors (mGluR-I), as well as the eukaryotic elongation factor-2 (eEF2)-dependent protein synthesis. The absence of mEPSCs results in presynaptic suppression of inhibitory synapses via protein synthesis-dependent elevation of eCB signaling.  This research reveals a critical role of miniature excitatory synaptic activities in maintaining inhibitory synaptic function, and a novel role of eCB signaling in the homeostatic regulation of synaptic activity.