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A. M. Fontainhas, K. J. Liang, P. Mettu, S. Chen, W. Li, R. N. Fariss, W. T. Wong; Retinal Neurotransmission Regulates Dendritic Morphology and Dynamic Behavior in Microglia. Invest. Ophthalmol. Vis. Sci. 2009;50(13):6254.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia are resident immune cells of the CNS that exhibit marked structural and morphological plasticity. The functional significance and regulation of microglial dynamism is not completely understood. Neurotransmission is a prominent form of endogenous intercellular communication occurring between neurons and glia in the retina. We investigated the effect of retinal neurotransmission on the microglial morphology.
Whole-mount retinal explants were acutely isolated from CX3CR1+/GFP mice, and cellular morphologies of GFP-labeled microglia were followed with time-lapse confocal imaging. Morphological analyses of microglia dendritic area and overall dendritic length were performed at baseline and in response to glutamatergic and GABAergic agonists and antagonists. Electrical responses of microglia in the inner retina to focal applications of agonists were also followed by patch-clamp electrophysiological recordings.
Whole-cell patch clamp recordings in ramified microglia revealed that microglia exhibit no spontaneous electrical currents and do not respond to direct application of either glutamate or GABA. Similarly, overall microglia morphology, measured in terms of dendritic area and length, was also unaffected by bath application of either agonist. Interestingly, blockade of glutamatergic and GABAergic receptors exerted significant effects. Non-NMDA glutamatergic receptor antagonist NBQX (10µM), and AMPA-receptor antagonist, GYKI (100µM), decreased overall dendritic area and total dendritic length significantly while NMDA receptor antagonist, AP5 (100µM), and kainate receptor antagonist, UBP302 (10µM), had little or no effects. Conversely, the GABA receptor antagonist, bicuculline (150µM), significantly increased total dendritic length.
Endogenous glutamatergic and GABAergic transmission in the retina coordinately regulate microglial morphology. Neurotransmitter regulation is likely to occur indirectly as microglia have little response to direct agonist application but do respond to their inhibition. These findings indicate that microglia are responsive to retinal neurotransmission, possibly mediated by an intermediary cell type or messenger.
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