The role of microglia and their CX3CR1 signaling in adult neurogenesis in the olfactory bulb

被引：80

作者：

Reshef, Ronen ^{[1
]}

Kudryavitskaya, Elena ^{[2
,3
]}

Shani-Narkiss, Haran ^{[2
,3
]}

Isaacson, Batya ^{[4
]}

Rimmerman, Neta ^{[1
]}

Mizrahi, Adi ^{[2
,3
]}

Yirmiya, Raz ^{[1
]}

机构：

[1] Hebrew Univ Jerusalem, Dept Psychol, Jerusalem, Israel

[2] Hebrew Univ Jerusalem, Inst Life Sci, Dept Neurobiol, Jerusalem, Israel

[3] Hebrew Univ Jerusalem, Edmond & Lily Safra Ctr Brain Sci, Jerusalem, Israel

[4] Hebrew Univ Jerusalem, Lautenberg Ctr Gen & Tumor Immunol, Dept Immunol & Canc Res, Jerusalem, Israel

来源：

ELIFE | 2017年 / 6卷

基金：

以色列科学基金会;

关键词：

BORN NEURONS; HIPPOCAMPAL NEUROGENESIS; SYNAPTIC INTEGRATION; PROGENITOR-CELL; IMMUNE CELLS; FRACTALKINE; EXPRESSION; PLASTICITY; CONNECTIVITY; INTERNEURONS;

D O I：

10.7554/eLife.30809

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Microglia play important roles in perinatal neuro- and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronal-microglial communication in CX3C receptor-1 deficient (Cx3cr1(-/-)) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination. Functionally, odor-evoked responses of mitral cells, which are normally inhibited by abGCs, were increased in microglia-depleted mice. In Cx3cr1(-/-) mice, abGCs exhibited reduced spine density, dynamics and size, concomitantly with reduced contacts between Cx3cr1-deficient microglia and abGCs' dendritic shafts, along with increased proportion of microglia-contacted spines. Thus, during adult neurogenesis, microglia regulate the elimination (pruning), formation, and maintenance of synapses on newborn neurons, contributing to the functional integrity of the olfactory bulb circuitry.

引用

页数：30

共 80 条

[1] Synaptic Inhibition in the Olfactory Bulb Accelerates Odor Discrimination in Mice [J].

Abraham, Nixon M. ;

Egger, Veronica ;

Shimshek, Derya R. ;

Renden, Robert ;

Fukunaga, Izumi ;

Sprengel, Rolf ;

Seeburg, Peter H. ;

Klugmann, Matthias ;

Margrie, Troy W. ;

Schaefer, Andreas T. ;

Kuner, Thomas .

NEURON, 2010, 65 (03) :399-411

[2] Functional transformations of odor inputs in the mouse olfactory bulb [J].

Adam, Yoav ;

Livneh, Yoav ;

Miyamichi, Kazunari ;

Groysman, Maya ;

Luo, Liqun ;

Mizrahi, Adi .

FRONTIERS IN NEURAL CIRCUITS, 2014, 8

[3] Long-Term Imaging Reveals Dynamic Changes in the Neuronal Composition of the Glomerular Layer [J].

Adam, Yoav ;

Mizrahi, Adi .

JOURNAL OF NEUROSCIENCE, 2011, 31 (22) :7967-7973

[4] Activation of adult-born neurons facilitates learning and memory [J].

Alonso, Mariana ;

Lepousez, Gabriel ;

Wagner, Sebastien ;

Bardy, Cedric ;

Gabellec, Marie-Madeleine ;

Torquet, Nicolas ;

Lledo, Pierre-Marie .

NATURE NEUROSCIENCE, 2012, 15 (06) :897-U127

[5] HTSeq-a Python']Python framework to work with high-throughput sequencing data [J].

Anders, Simon ;

Pyl, Paul Theodor ;

Huber, Wolfgang .

BIOINFORMATICS, 2015, 31 (02) :166-169

[6] Count-based differential expression analysis of RNA sequencing data using R and Bioconductor [J].

Anders, Simon ;

McCarthy, Davis J. ;

Chen, Yunshun ;

Okoniewski, Michal ;

Smyth, Gordon K. ;

Huber, Wolfgang ;

Robinson, Mark D. .

NATURE PROTOCOLS, 2013, 8 (09) :1765-1786

[7] Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats [J].

Bachstetter, Adam D. ;

Morganti, Josh M. ;

Jernberg, Jennifer ;

Schlunk, Andrea ;

Mitchell, Staten H. ;

Brewster, Kaelin W. ;

Hudson, Charles E. ;

Cole, Michael J. ;

Harrison, Jeffrey K. ;

Bickford, Paula C. ;

Gemma, Carmelina .

NEUROBIOLOGY OF AGING, 2011, 32 (11) :2030-2044

[8] Controlling the false discovery rate in behavior genetics research [J].

Benjamini, Y ;

Drai, D ;

Elmer, G ;

Kafkafi, N ;

Golani, I .

BEHAVIOURAL BRAIN RESEARCH, 2001, 125 (1-2) :279-284

[9] RETRACTED: TGF-β signaling regulates neuronal Clq expression and developmental synaptic refinement (Retracted Article) [J].

Bialas, Allison R. ;

Stevens, Beth .

NATURE NEUROSCIENCE, 2013, 16 (12) :1773-1782

[10] Principal cell activity induces spine relocation of adult-born interneurons in the olfactory bulb [J].

Breton-Provencher, Vincent ;

Bakhshetyan, Karen ;

Hardy, Delphine ;

Bammann, Rodrigo Roberto ;

Cavarretta, Francesco ;

Snapyan, Marina ;

Cote, Daniel ;

Migliore, Michele ;

Saghatelyan, Armen .

NATURE COMMUNICATIONS, 2016, 7

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