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The Journal of Neuroscience, November 19, 2008, 28(47):12477-12488; doi:10.1523/JNEUROSCI.3240-08.2008

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Development/Plasticity/Repair
Inflammation Regulates Functional Integration of Neurons Born in Adult Brain

Katherine Jakubs,^1,4 * Sara Bonde,^1,4 * Robert E. Iosif,^1,4 Christine T. Ekdahl,^1,4,5 Zaal Kokaia,^3,4 Merab Kokaia,^2,4 and Olle Lindvall^1,4

¹Laboratory of Neurogenesis and Cell Therapy and ²Experimental Epilepsy Group, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, ³Laboratory of Neural Stem Cell Biology, Section of Restorative Neurology, University Hospital, and ⁴Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, SE-221 84 Lund, Sweden, and ⁵Division of Clinical Neurophysiology, University Hospital, SE-221 85 Lund, Sweden

Correspondence should be addressed to Dr. Olle Lindvall, Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden. Email: olle.lindvall{at}med.lu.se

Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA_A receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.

Key words: adult neurogenesis; inflammation; synaptic plasticity; gephyrin; electrophysiology; hippocampus

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Received July 11, 2008; revised Sept. 30, 2008; accepted Oct. 4, 2008.

Correspondence should be addressed to Dr. Olle Lindvall, Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden. Email: olle.lindvall{at}med.lu.se

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				C. D. Keene, R. Chang, C. Stephen, M. Nivison, S. E. Nutt, A. Look, R. M. Breyer, P. J. Horner, R. Hevner, and T. J. Montine Protection of Hippocampal Neurogenesis from Toll-Like Receptor 4-Dependent Innate Immune Activation by Ablation of Prostaglandin E2 Receptor Subtype EP1 or EP2 Am. J. Pathol., June 1, 2009; 174(6): 2300 - 2309. [Abstract] [Full Text] [PDF]

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