TY - JOUR
T1 - Typical development of synaptic and neuronal properties can proceed without microglia in the cortex and thalamus
AU - O'Keeffe, Mary
AU - Booker, Sam A
AU - Walsh, Darren
AU - Li, Mosi
AU - Henley, Chloe
AU - Simões De Oliveira, Laura
AU - Liu, Mingshan
AU - Wang, Xingran
AU - Banqueri Lopez, Maria
AU - Ridley, Katherine
AU - Dissanayake, Kosala
AU - Martinez Gonzalez, Cristina
AU - Craigie, Kirsty J.
AU - Vasoya, Deepali
AU - Leah, Tom
AU - He, Xin
AU - Hume, David A.
AU - Duguid, Ian
AU - Nolan, Matthew F
AU - Qiu, Jing
AU - Wyllie, David J. A.
AU - Dando, Owen
AU - Gonzalez-Sulser, Alfredo
AU - Gan, Jian
AU - Pridans, Clare
AU - Kind, Peter C
AU - Hardingham, Giles E.
PY - 2025/1/6
Y1 - 2025/1/6
N2 - Brain-resident macrophages, microglia, have been proposed to play an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that a variety of neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse which lacks microglia (Csf1rΔFIRE/ΔFIRE) we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single cell/nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation due to microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.
AB - Brain-resident macrophages, microglia, have been proposed to play an active role in synaptic refinement and maturation, influencing plasticity and circuit-level connectivity. Here we show that a variety of neurodevelopmental processes previously attributed to microglia can proceed without them. Using a genetically modified mouse which lacks microglia (Csf1rΔFIRE/ΔFIRE) we find that intrinsic properties, synapse number and synaptic maturation are largely normal in the hippocampal CA1 region and somatosensory cortex at stages where microglia have been implicated. Seizure susceptibility and hippocampal-prefrontal cortex coherence in awake behaving animals, processes disrupted in mice deficient in microglia-enriched genes, are also normal. Similarly, eye-specific segregation of inputs into the lateral geniculate nucleus proceeds normally in the absence of microglia. Single cell/nucleus transcriptomic analyses of neurons and astrocytes did not uncover any substantial perturbation due to microglial absence. Thus, the brain possesses remarkable adaptability to execute developmental synaptic refinement, maturation and connectivity in the absence of microglia.
U2 - 10.1038/s41593-024-01833-x
DO - 10.1038/s41593-024-01833-x
M3 - Article
SN - 1097-6256
SP - 1
EP - 12
JO - Nature Neuroscience
JF - Nature Neuroscience
ER -