Department of Pathology, Children's Hospital Boston, Boston, MA, 02115, USA.
Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA.
Sci Rep. 2022 Jul 27;12(1):12779. doi: 10.1038/s41598-022-15503-0.
Microglia contain multiple mechanisms that shape the synaptic landscape during postnatal development. Whether the synaptic changes mediated by microglia reflect the developmental refinement of neuronal responses in sensory cortices, however, remains poorly understood. In postnatal life, the development of increased orientation and spatial frequency selectivity of neuronal responses in primary visual cortex (V1) supports the emergence of high visual acuity. Here, we used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to rapidly and durably deplete microglia in mice during the juvenile period in which increased orientation and spatial frequency selectivity emerge. Excitatory and inhibitory tuning properties were measured simultaneously using multi-photon calcium imaging in layer II/III of mouse V1. We found that microglia depletion generally increased evoked activity which, in turn, reduced orientation selectivity. Surprisingly, microglia were not required for the emergence of high spatial frequency tuned responses. In addition, microglia depletion did not perturb cortical binocularity, suggesting normal depth processing. Together, our finding that orientation and high spatial frequency selectivity in V1 are differentially supported by microglia reveal that microglia are required normal sensory processing, albeit selectively.
小胶质细胞包含多种机制，可在出生后发育过程中塑造突触景观。然而，小胶质细胞介导的突触变化是否反映了感觉皮层中神经元反应的发育精细化，仍知之甚少。在出生后，初级视觉皮层（V1）中神经元反应的朝向和空间频率选择性增加的发展支持了高视觉敏锐度的出现。在这里，我们在幼年时期（即朝向和空间频率选择性增加的时期）使用集落刺激因子 1 受体（CSF1R）抑制剂 PLX5622 快速且持久地耗尽小鼠的小胶质细胞。使用多光子钙成像在小鼠 V1 的 II/III 层中同时测量兴奋性和抑制性调谐特性。我们发现小胶质细胞耗竭通常会增加诱发活动，从而降低朝向选择性。令人惊讶的是，小胶质细胞对于高空间频率调谐反应的出现并不是必需的。此外，小胶质细胞耗竭不会扰乱皮层双眼性，表明正常的深度处理。总之，我们发现 V1 中的朝向和高空间频率选择性由小胶质细胞以不同的方式支持，这表明小胶质细胞是正常感觉处理所必需的，尽管是选择性的。
