Microglia promote learning-dependent synapse formation through BDNF

By Christopher N. Parkhurst, Guang Yang, I. Ninan, J. Savas, John R. Yates III, J. Lafaille, B. Hempstead, Dan R. Littman, Wen-Biao Gan. Cell, 2013

2,288 citations recorded by the source corpus.

SUMMARY Microglia are the resident macrophages of the central nervous system and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1CreER mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1CreER to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia show deficits in multiple learning tasks and a significant reduction in motor learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal TrkB phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal important physiological functions of microglia in learning and memory by promoting learning-related synapse formation through BDNF signaling.

Subfields: Cellular and Molecular Neuroscience, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/61fdc463c3b3b87df2b2ab58e38882933a149f9d

How researchers see this paper

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In Cellular and Molecular Neuroscience

1. M. Pekny
2. M. Pekna
3. B. Barres
4. Beth Stevens
5. L. Colucci-D'Amato
6. Irving L. Weissman
7. E. Huang
8. William W. Seeley

In Neurology

1. M. Pekny
2. M. Pekna
3. B. Barres
4. Beth Stevens
5. Florent Ginhoux
6. Chao Gao
7. Shengdi Chen
8. Yuyan Tan

In Physiology

1. M. Pekny
2. M. Pekna
3. Beth Stevens
4. Bruce L. Miller
5. S. A. Liddelow
6. E. Huang
7. William W. Seeley
8. Eileen Bigio

Citations in the corpus

• Self-renewing resident cardiac macrophages limit adverse remodeling following myocardial infarction (2018, positive): “Prior studies have shown robust TAM-inducible reporter gene expression in Cx3cr1-expressing resident macrophages, and transient labeling of blood monocytes 13, 26, 27 .”
• Progranulin Deficiency Promotes Circuit-Specific Synaptic Pruning by Microglia via Complement Activation (2016, positive): “Finally, genetic ablation of microglia in the adult brain further reveals the essential role of microglia in the maintenance of synaptic functions and motor learning (Parkhurst et al., 2013).”
• New tools for studying microglia in the mouse and human CNS (2016, background): “The generation of knockin Cx3cr1-GFP (10) and Cx3cr1-CreERT (11, 12) mice advanced the specificity and sophistication with which to study microglial function.”