Review Article Microglia Control Neuronal Network Excitability via BDNF Signalling

Copyright © 2013 F. Ferrini and Y. De Koninck.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Microglia-neuron interactions play a crucial role in several neurological disorders characterized by altered neural network excitability, such as epilepsy and neuropathic pain. While a series of potential messengers have been postulated as substrates of the communication between microglia and neurons, including cytokines, purines, prostaglandins, and nitric oxide, the specific links betweenmessengers, microglia, neuronal networks, and diseases have remained elusive. Brain-derived neurotrophic factor (BDNF) released bymicroglia emerges as an exception in this riddle. Here, we review the current knowledge on the role played bymicroglial BDNF in controlling neuronal excitability by causing disinhibition.The efforts made by different laboratories during the last decade have collectively provided a robust mechanistic paradigm which elucidates the mechanisms involved in the synthesis and release of BDNF frommicroglia, the downstream TrkB-mediated signals in neurons, and the biophysical mechanism by which disinhibition occurs, via the downregulation of the K+-Cl − cotransporter KCC2, dysrupting Cl − homeostasis, and hence the strength of GABAA-and glycine receptor-mediated inhibition.The resulting altered network activity appears to explain several features of the associated pathologies. Targeting the molecular players involved in this canonical signaling pathway may lead to novel therapeutic approach for ameliorating a wide array of neural dysfunctions. 1