Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.

To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits.

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.

Natural binocular depth discrimination behavior in mice explained by visual cortical activity.

In mice and other mammals, forebrain neurons integrate right and left eye information to generate a three-dimensional representation of the visual environment. Neurons in the visual cortex of mice are sensitive to binocular disparity,1-3 yet it is unclear whether that sensitivity is linked to the perception of depth.4-8 We developed a natural task based on the classic visual cliff and pole descent tasks to estimate the psychophysical range of mouse depth discrimination.5,9 Mice with binocular vision descended to a near (shallow) surface more often when surrounding far (deep) surfaces were progressively more distant. Occlusion of one eye severely impaired their ability to target the near surface. We quantified the distance at which animals make their decisions to estimate the binocular image displacement of the checkerboard pattern on the near and far surfaces. Then, we assayed the disparity sensitivity of large populations of binocular neurons in primary visual cortex (V1) using two-photon microscopy2 and quantitatively compared this information available in V1 to their behavioral sensitivity. Disparity information in V1 matches the behavioral performance over the range of depths examined and was resistant to changes in binocular alignment. These findings reveal that mice naturally use stereoscopic cues to guide their behavior and indicate a neural basis for this depth discrimination task.

Layer 4 Gates Plasticity in Visual Cortex Independent of a Canonical Microcircuit.

Disrupting binocular vision during a developmental critical period can yield enduring changes to ocular dominance (OD) in primary visual cortex (V1). Here we investigated how this experience-dependent plasticity is coordinated within the laminar circuitry of V1 by deleting separately in each cortical layer (L) a gene required to close the critical period, nogo-66 receptor (ngr1). Deleting ngr1 in excitatory neurons in L4, but not in L2/3, L5, or L6, prevented closure of the critical period, and adult mice remained sensitive to brief monocular deprivation. Intracortical disinhibition, but not thalamocortical disinhibition, accompanied this OD plasticity. Both juvenile wild-type mice and adult mice lacking ngr1 in L4 displayed OD plasticity that advanced more rapidly L4 than L2/3 or L5. Interestingly, blocking OD plasticity in L2/3 with the drug AM-251 did not impair OD plasticity in L5. We propose that L4 restricts disinhibition and gates OD plasticity independent of a canonical cortical microcircuit.