Juvenile depletion of microglia reduces orientation but not high spatial frequency selectivity in mouse V1
Dario X Figueroa Velez1, Miguel Arreola2, Carey Y L Huh2
1Department of Pathology, Children's Hospital Boston, Boston, MA, 02115, USA.
Abstract:
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.
Insights
Microglia depletion in juvenile mice reduced orientation selectivity in the visual cortex but did not affect spatial frequency tuning or binocularity. This suggests microglia selectively support certain aspects of sensory processing.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Microglia play a crucial role in shaping neural circuits during development.
- The specific contribution of microglia to the refinement of neuronal responses in sensory cortices is not fully understood.
- Development of orientation and spatial frequency selectivity in the primary visual cortex (V1) is critical for visual acuity.
Purpose of the Study:
- To investigate the role of microglia in the emergence of orientation and spatial frequency selectivity in the mouse primary visual cortex (V1).
- To determine whether microglia are essential for normal sensory processing during the juvenile period.
Main Methods:
- Utilized colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 for rapid and durable microglia depletion in juvenile mice.
- Employed multi-photon calcium imaging to simultaneously measure excitatory and inhibitory tuning properties in layer II/III of mouse V1.
- Assessed changes in evoked activity, orientation selectivity, spatial frequency tuning, and cortical binocularity.
Main Results:
- Microglia depletion led to increased evoked activity and reduced orientation selectivity in V1.
- Surprisingly, microglia were not essential for the development of high spatial frequency tuned responses.
- Microglia depletion did not affect cortical binocularity, indicating normal depth processing.
Conclusions:
- Microglia are selectively required for normal sensory processing in the visual cortex.
- Orientation selectivity and high spatial frequency tuning in V1 are differentially dependent on microglia.
- These findings highlight the nuanced role of microglia in refining neuronal responses during critical developmental periods.
