Early Monocular Defocus Disrupts the Normal Development of Receptive-Field Structure in V2 Neurons of Macaque Monkeys

Abstract

Experiencing different quality images in the two eyes soon after birth can cause amblyopia, a developmental vision disorder. Amblyopic humans show the reduced capacity for judging the relative position of a visual target in reference to nearby stimulus elements (position uncertainty) and often experience visual image distortion. Although abnormal pooling of local stimulus information by neurons beyond striate cortex (V1) is often suggested as a neural basis of these deficits, extrastriate neurons in the amblyopic brain have rarely been studied using microelectrode recording methods. The receptive field (RF) of neurons in visual area V2 in normal monkeys is made up of multiple subfields that are thought to reflect V1 inputs and are capable of encoding the spatial relationship between local stimulus features. We created primate models of anisometropic amblyopia and analyzed the RF subfield maps for multiple nearby V2 neurons of anesthetized monkeys by using dynamic two-dimensional noise stimuli and reverse correlation methods. Unlike in normal monkeys, the subfield maps of V2 neurons in amblyopic monkeys were severely disorganized: subfield maps showed higher heterogeneity within each neuron as well as across nearby neurons. Amblyopic V2 neurons exhibited robust binocular suppression and the strength of the suppression was positively correlated with the degree of hereogeneity and the severity of amblyopia in individual monkeys. Our results suggest that the disorganized subfield maps and robust binocular suppression of amblyopic V2 neurons are likely to adversely affect the higher stages of cortical processing resulting in position uncertainty and image distortion.

Observations on the relationship between anisometropia, amblyopia and strabismus

“…On the other hand, as previously observed in both macaques (Hung et al, 1995, Smith III et al, 1985, Smith III et al, 1999, Tao et al, 2014) and marmosets (Graham & Judge, 1999, Troilo et al, 2009, Whatham & Judge, 2001a), the results obtained using spectacle lens strategies to impose hyperopic anisometropia or contact lens regimens that were specifically designed to avoid corneal alterations demonstrate that chronic hyperopic defocus consistently produces compensating axial myopia in the defocused eye. Moreover, imposed hyperopic anisometropias can produce amblyopia and the degree of amblyopia is strongly correlated with the magnitude of imposed hyperopic anisometropia that an animal experiences early in life (Smith III et al, 1985, Smith III et al, 1999, Tao et al, 2014).…”

“…In panels A–C, the interocular differences in refractive error are plotted as a function of age for individual animals that were reared with either monocular spectacle diffusers (A), monocular powered contact lenses (B) or monocular powered spectacle lenses (C). All of these animals had behaviorally confirmed functional amblyopia in their treated eyes (Smith III et al, 2000, Smith III et al, 1985, Smith III et al, 1999, Tao et al, 2014). The average (±SD) interocular grating acuity ratios (treated eye/fellow eye) for the monkeys in panels A, B, and C, were 0.24 ± 0.22, 0.50 ± 0.24 and 0.58 ± 0.23, respectively.…”

“…Because abnormal visual experience can produce neural changes associated with strabismus and amblyopia in a relatively short period of time (Freeman & Olson, 1982, Olson & Freeman, 1975, Tao, Zhang, Shen, Wensveen, Smith III, Nishimoto, Ohzawa & Chino, 2014, Wang, Zhang, Tao, Wensveen, Smith III & Chino, 2017, Zhang, Bi, Sakai, Maruko, Zheng, Smith & Chino, 2005), certainly before the hyperopic anisometropias can be observed, and because the degree of hyperopic anisometropia was correlated with the degree of amblyopia in contact-lens-reared monkeys, it has been argued that the amblyopia occurred first, which subsequently altered eye growth producing hyperopic shifts in refractive error (Barrett et al, 2013, Kiorpes & Wallman, 1995). In essence, this conclusion implies that the normal emmetropizing responses to hyperopic defocus were overridden by the presence of amblyopia.…”

“…Moreover, imposed hyperopic anisometropias can produce amblyopia and the degree of amblyopia is strongly correlated with the magnitude of imposed hyperopic anisometropia that an animal experiences early in life (Smith III et al, 1985, Smith III et al, 1999, Tao et al, 2014). Thus, the results from animals experiments provide strong support for the concept that uncorrected hyperopic anisometropia promotes the development of amblyopia in young children and that the depth of amblyopia will increase with the degree of hyperopic anisometropia, an association that is well established in children (Barrett et al, 2013, Granet et al, 2006, Levi et al, 2011, Weakley, 1999).…”

Population representation of visual information in areas V1 and V2 of amblyopic macaques

“…This must reflect a disordering of afferent connectivity, leading to a disruption of the structure of cortical receptive fields, and serves as a simple example of information loss due to abnormal pooling of normal visual signals. There is similar evidence that fine spatial structure of receptive fields may become disorganized in the transformation between V1 and V2 of amblyopic macaques (Tao, et al, 2014). The performance of our decoding algorithm depends on optimal combination of neural signals, and an instantiation of this algorithm in the brain requires precise connections between early visual cortex and higher areas.…”