title: Inflammation regulates functional integration of neurons born in adult brain.
abstract: 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.
authors.affiliation: Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden.
authors.forename: Katherine
authors.initials: K
authors.lastname: Jakubs
authors.forename: Sara
authors.initials: S
authors.lastname: Bonde
authors.forename: Robert E
authors.initials: RE
authors.lastname: Iosif
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
authors.forename: Merab
authors.initials: M
authors.lastname: Kokaia
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D049229:Dendritic Spines / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D053331:Ectodysplasins / Q000378:metabolism; D004558:Electric Stimulation; D004569:Electroencephalography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008070:Lipopolysaccharides; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D018613:Microscopy, Confocal / Q000379:methods; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D053331:Ectodysplasins; D018691:Excitatory Amino Acid Antagonists; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D011810:Quinoxalines; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; C013411:biocytin; D008239:Lysine