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Oakes, D. K.

Publications and source records attributed to Oakes, D. K..

2 recordsLinked to original sources

A mouse model for cerebral/cortical visual impairment (CVI) impairs vision and disrupts the spatial frequency tuning of neurons in visual cortex

Cerebral/cortical visual impairment (CVI) is a visual disorder associated with perinatal hypoxic injury. The pathophysiology of CVI is poorly understood in part because of the lack of an animal model. Here we developed a murine model of CVI from existing rodent early postnatal hypoxia models for periventricular leukomalacia. Exposure to hypoxia during the equivalent to the human third trimester did not perturb motor function but caused severe impairments in binocular depth perception and visual acuity. Impaired vision was associated with normal retinal function, but reduced size of the visual thalamus, and aberrant tuning for spatial frequency by populations of excitatory neurons in primary visual cortex. This murine model of CVI provides a framework for triangulating circuit deficits with specific visual impairments and testing potential therapeutic interventions.

neuroscience↗

Microglia are dispensable for experience-dependent refinement of visual circuitry

Microglia are proposed to be critical for the refinement of developing neural circuitry. However, evidence identifying specific roles for microglia has been limited and often indirect. Here we examined whether microglia are required for the experience-dependent refinement of visual circuitry and visual function during development. We ablated microglia by administering the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622, and then examined the consequences for retinal function, receptive field tuning of neurons in primary visual cortex (V1), visual acuity, and experience-dependent plasticity in visual circuitry. Eradicating microglia by treating mice with PLX5622 beginning at postnatal day (P) 14 did not alter visual response properties of retinal ganglion cells examined three or more weeks later. Mice treated with PLX5622 from P14 lacked more than 95% of microglia in V1 by P18, prior to the opening of the critical period. Despite the absence of microglia, the receptive field tuning properties of neurons in V1 were normal at P32. Similarly, eradicating microglia did not affect the maturation of visual acuity. Mice treated with PLX5622 displayed typical ocular dominance plasticity in response to brief monocular deprivation. Thus, none of these principal measurements of visual circuit development and function detectibly differed in the absence of microglia. We conclude that microglia are dispensable for experience-dependent refinement of visual circuitry. These findings challenge the proposed critical role of microglia in refining neural circuitry.

neuroscience↗