Biology subjects

Attaway, C. A.

Publications and source records attributed to Attaway, C. A..

4 recordsLinked to original sources

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

Gene augmentation therapy treats mature mice with complete congenital stationary night blindness (cCSNB), improving retinal function and visual acuity

Recombinant adeno-associated virus (rAAV) mediated gene therapy is an effective approach for targeting therapeutic genes to retinal photoreceptors. Complete congenital stationary night blindness (cCSNB) is a genetically heterogeneous inherited retinal disease caused by mutations in one of several genes, which are part of a large and interdependent depolarizing bipolar cell (DBC) signalplex required for normal synaptic signaling with photoreceptors. These genes include NYX, GRM6, TRPM1, GPR179, and LRIT3, and the cCSNB phenotype that results is characterized by abnormal low light vision, myopia, and nystagmus, but does not include retinal degeneration. Because of the non-progressive and recessive nature of cCSNB we investigated the potential of a gene augmentation approach in the mature retina to improve retinal function and visual acuity. We used a mouse model of cCSNB caused by the loss of LRIT3 to evaluate the efficacy of a single subretinal injection of rAAV expressing LRIT3 in either rods or cones, and the extent of restoration of retinal function and visual acuity. We show that gene augmentation by expressing LRIT3 in the rods of mature Lrit3-/- retinas restores function and scotopic visual acuity, and when expressed on cones, improves both photopic and scotopic visual acuity.

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↗