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CSF-1 controls cerebellar microglia and is required for motor function and social interaction

Veronika Kana1,2,3, Fiona A Desland1,2,3, Maria Casanova-Acebes1,2,3

  • 1Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY.

The Journal of Experimental Medicine
|July 28, 2019
PubMed

Insights

Cerebellar microglia have a unique molecular identity driven by CSF-1, crucial for motor learning and social behavior. Their depletion impairs Purkinju cells and neuronal function.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the brain's resident macrophages, are vital for shaping neuronal circuits in the forebrain.
  • The specific roles and characteristics of microglia within the cerebellum remain largely unexplored.

Purpose of the Study:

  • To investigate the unique molecular identity and function of cerebellar microglia.
  • To elucidate the signaling pathways regulating cerebellar microglial identity and their impact on neuronal circuits and behavior.

Main Methods:

  • Comparative transcriptomic analysis of human and mouse cerebellar microglia versus forebrain microglia.
  • Genetic manipulation to deplete CSF-1 in Nestin-expressing cells and assess effects on microglia.
  • Assessment of Purkinje cell numbers, neuronal function, motor learning, and social novelty interactions.

Main Results:

  • Cerebellar microglia exhibit a distinct molecular signature compared to forebrain microglia, driven by CSF-1 (colony-stimulating factor 1).
  • CSF-1, not IL-34, is essential for maintaining cerebellar microglial populations and their transcriptional profile.
  • CSF-1 depletion led to cerebellar microglial reduction, Purkinje cell loss, impaired neuronal function, and deficits in motor learning and social behavior.

Conclusions:

  • Cerebellar microglial identity is regulated by a unique CSF-1/CSF-1R signaling pathway.
  • This pathway is critical for maintaining cerebellar integrity, neuronal function, motor learning, and social behaviors.

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