QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 21, 2009, 29(42):13222-13231; doi:10.1523/JNEUROSCI.1710-09.2009

This Article Full Text Full Text (PDF) Supplemental Material Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Zhang, S.-y. Articles by Zhang, X.-h. PubMed PubMed Citation Articles by Zhang, S.-y. Articles by Zhang, X.-h.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Endocannabinoid-Dependent Homeostatic Regulation of Inhibitory Synapses by Miniature Excitatory Synaptic Activities

Si-yu Zhang,^1 * Min Xu,^1 * Qing-long Miao,¹ Mu-ming Poo,^1,2 and Xiao-hui Zhang¹

¹Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China, and ²Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720

Correspondence should be addressed to either of the following: Mu-ming Poo, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, Email: mpoo{at}berkeley.edu; or Xiao-hui Zhang, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China. E-mail: Email: xhzhang{at}ion.ac.cn

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 EPSCs (mEPSCs) for a few hours is known to cause upregulation of excitatory synaptic strength, suggesting that mEPSCs contribute to the maintenance of excitatory synaptic functions. In the present study, we found that the absence of mEPSCs for 1–3 h also resulted 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 IPSCs (mIPSCs) as well as the reduced amplitude of IPSCs. This homeostatic regulation depended on endocannabinoid (eCB) signaling, because blockade of either the activation of cannabinoid type-1 receptors (CB1Rs) or the synthesis of its endogenous ligand 2-arachidonoylglycerol (2-AG) abolished the suppression of inhibitory synapses caused by the absence of mEPSCs. Blockade of group I metabotropic glutamate receptors (mGluR-I) also abolished the suppression of inhibitory synapses, consistent with the mGluR-I requirement for eCB synthesis and release in cortical synapses. Furthermore, this homeostatic regulation also required eukaryotic elongation factor-2 (eEF2)-dependent protein synthesis, but not gene transcription. Activation of eEF2 alone was sufficient to suppress the mIPSC frequency, an effect abolished by inhibiting CB1Rs. Thus, mEPSCs contribute to the maintenance of inhibitory synaptic function and the absence of mEPSCs results in presynaptic suppression of inhibitory synapses via protein synthesis-dependent elevation of eCB signaling.

---

Received April 9, 2009; revised Aug. 24, 2009; accepted Sept. 15, 2009.

Correspondence should be addressed to either of the following: Mu-ming Poo, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200, Email: mpoo{at}berkeley.edu; or Xiao-hui Zhang, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China. E-mail: Email: xhzhang{at}ion.ac.cn

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help