Biology subjects

McGee, A. W.

Publications and source records attributed to McGee, A. W..

8 recordsLinked to original sources

bioRxiv2026

Neuropil aggrecan, not perineuronal nets, closes the critical period for visual plasticity

Perineuronal nets (PNNs) are widely reported to close developmental critical periods and restrict experience-dependent plasticity. Here we tested this model by selectively eliminating gene expression for aggrecan (Acan), an essential component of PNNs. In visual cortex, PNNs predominantly ensheath parvalbumin-positive (PV+) interneurons. Deletion of Acan in inhibitory neurons eliminated PNNs but did not prevent closure of the critical period. By comparison, deletion of Acan in all neurons, or only in excitatory forebrain neurons, sustained critical-period plasticity in adult mice. Visual plasticity in adults was associated with reduced cortical excitatory synaptic inputs onto layer 2/3 PV+ interneurons and increased expression of some immediate early genes in visual cortex but normal response strength and tuning properties of layer 2/3 excitatory neurons. These findings rectify long-standing models that misattribute closure of the critical period to PNNs and identify that aggrecan expressed by excitatory neurons resident in the surrounding neuropil limits visual plasticity.

neuroscience↗

bioRxiv2025

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↗

bioRxiv2025

Enhancing experience-dependent plasticity accelerates vision loss in a murine model of retinitis pigmentosa

Modulating neural plasticity is pursued as a therapeutic approach for several neurologic conditions. Here we evaluated if enhancing experience-dependent plasticity prolongs vision in a murine model of retinitis pigmentosa. First, we quantified the loss of visual acuity under both scotopic and photopic conditions for mice heterozygous for the P23H mutation in the Rhodopsin gene (Rho P23H/+). Acuity progressively declined under scotopic conditions followed by photopic conditions. Acuity deficits only broadly correlated with the retinal response measured by the electroretinogram. In contrast, acuity deficits were consistent with the percent of cortical excitatory layer 2/3 neurons responsive to higher spatial frequency visual stimuli. Then, we tested if enhancing plasticity in adult visual circuity by deleting the nogo-66 receptor gene (Ngr1) would preserve vision in Rho P23H/+ mice. However, loss of vision was accelerated in Ngr1 -/-; Rho P23H/+ mice. Thus, enhancing plasticity can be maladaptive in the context of neural degeneration.

neuroscience↗

bioRxiv2025

Degraded mapping of disparity tuning in visual cortex explains deficits in binocular depth perception

Sensory cortex is highly organized, but the function of this organization is contentious. We show that closing one eye during the developmental critical period in juvenile mice (monocular deprivation) caused lasting impairments in binocular depth perception and disrupted cortical maps of binocular disparity tuning. In normal mice, disparity tuning was concentrated in the central visual field, particularly with respect to azimuth and in higher visual areas (HVAs). Additionally, neurons transitioned from encoding nearer to farther stereoscopic depths from the center toward the peripheral visual field, especially along elevation and within HVAs. Monocular deprivation did not reduce overall disparity selectivity across the neuronal population, but rather weakened the retinotopic and hierarchical organization of disparity tuning and reduced trial-to-trial reliability of neuronal responses. Analysis of single-trial responses from neurons tuned to near disparities showed that this reduced response reliability is sufficient to explain the impaired depth discrimination observed in deprived mice.

neuroscience↗

bioRxiv2025

Experience directs the instability of neuronal tuning for critical period plasticity in mouse visual cortex

Brief monocular deprivation during a developmental critical period, but not thereafter, alters the receptive field properties (tuning) of neurons in visual cortex, but the characteristics of neural circuitry that permit this experience-dependent plasticity are largely unknown. We performed repeated calcium imaging at neuronal resolution to track the tuning properties of populations of excitatory layer 2/3 neurons in mouse visual cortex during or after the critical period, as well as in nogo-66 receptor (ngr1) mutant mice that sustain critical-period plasticity as adults. The instability of tuning for populations of neurons was greater in juvenile mice and adult ngr1 mutant mice. We propose instability of neuronal tuning gates plasticity and is directed by experience to alter the tuning of neurons during the critical period.

neuroscience↗

bioRxiv2023

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↗

bioRxiv2022

Structural remodeling of peripheral taste neurons is fast and independent of taste cell turnover

Taste bud cells are constantly replaced in taste buds as old cells die and new cells migrate into the bud. The perception of taste relies on new taste bud cells integrating with existing neural circuitry, yet how these new cells connect with a taste ganglion neuron is unknown. Do taste ganglion neurons remodel to accommodate taste bud cell renewal? If so, how much of the taste axon structure is fixed and how much remodels? Here we measured the motility and branching of individual taste arbors (the portion of the axon innervating taste buds) over time with two-photon in vivo microscopy. Terminal branches of taste arbors continuously and rapidly remodel within the taste bud. This remodeling is faster than predicted by taste bud cell renewal, with terminal branches added and lost concurrently. Surprisingly, ablating new taste cells with chemotherapeutic agents revealed that remodeling of the terminal branches of taste arbors does not rely of the renewal of taste bud cells. Although the arbor structure remodeling was fast and intrinsically controlled, no new arbors were added, and few were lost over 100 days. Taste ganglion neurons maintain a stable number of nerve arbors that are each capable of high-speed remodeling. Arbor structural plasticity would permit arbors to locate new taste bud cells, while stability of arbor number could support constancy in the degree of connectivity and function for each neuron over time.

neuroscience↗

bioRxiv2022

Monocular deprivation during the critical period alters neuronal tuning and the composition of visual circuitry

Abnormal visual experience during a developmental critical period degrades cortical responsiveness. Yet how experience-dependent plasticity alters the response properties of individual neurons and composition of visual circuitry is unclear. Here we measured with calcium imaging in alert mice how monocular deprivation (MD) during the developmental critical period affects binocularity, orientation, and spatial frequency tuning for neurons in primary visual cortex. Tracking the tuning properties for several hundred neurons revealed that the interconversion of monocular and binocular neurons relies on the quality of visual experience to determine the ratio of monocular neurons responsive to the contralateral and ipsilateral eye. In addition, a population of neurons more responsive to the closed eye were exchanged for neurons with tuning properties more similar to the responsive neurons altered by MD. Thus, plasticity during the critical period adapts to recent experience by both altering the tuning of responsive neurons and recruiting neurons with matching tuning properties.

neuroscience↗