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PRECIS Characteristics of the most mentioned glaucoma articles on the internet were analyzed, allowing a better understanding of the dissemination of glaucoma research to the general public. PURPOSE To determine the 100 most mentioned articles on the internet in the field of glaucoma and analyze their characteristics. MATERIALS AND METHODS We identified the top 100 glaucoma articles with the highest Altmetric Attention Score (AAS), an automatically calculated metric for monitoring social media. Each article was evaluated for several characteristics including year of publication, title, journal name, journal impact factor (IF), article topic, article type, affiliation, and online mentions (news, blog, policy, Twitter, Facebook, etc). Correlation analysis was conducted for AAS with these characteristics. RESULTS The selected 100 articles came from 44 journals with more than half (56%) published in ophthalmology-specific journals. There was no significant correlation between IF and number of articles in a specific journal or AAS (P>0.1), but the number of articles in the top 100 was higher for ophthalmology journals with a higher IF (P

Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in layer 2/3 neurons of adult male and female primary visual cortex in the MECP2-duplication syndrome animal model of autism. Increased response reliability was due in part to decreased response amplitude, decreased fluctuations in endogenous activity, and an abnormal decoupling of visual-evoked activity from endogenous activity. Similar to what was observed neuronally, the optokinetic reflex occurred more reliably at low contrasts in mutant mice compared with controls. Retinal responses did not explain our observations. These data suggest that the circuit mechanisms for combining sensory-evoked and endogenous signal and noise processes may be altered in this form of syndromic autism. SIGNIFICANCE STATEMENT Atypical sensory processing is now thought to be a core feature of the autism spectrum. Influential theories have proposed that both increased and decreased neural response reliability within sensory systems could underlie altered sensory processing in autism. Here, we report evidence for abnormally increased reliability of visual-evoked responses in primary visual cortex of the animal model for MECP2-duplication syndrome, a high-penetrance single-gene cause of autism. Visual-evoked activity was abnormally decoupled from endogenous activity in mutant mice, suggesting in line with the influential “hypo-priors” theory of autism that sensory priors embedded in endogenous activity may have less influence on perception in autism.

Retinal ganglion cells (GCs) are important visual neurons which carry complex spatiotemporal information from the retina to higher visual centers in the brain. By taking advantage of pathway-specific knockout/mutant mice and multi-electrode array (MEA) recording techniques, we analyze contributions of rod and cone pathways to responsiveness, kinetics and receptive field profiles of GCs under scotopic and photopic conditions. Our data suggest: (1) Scotopic responses of some GCs require all three rod pathways, some require only the secondary and tertiary rod pathways, and others require only the tertiary rod pathway. (2) There are more responsive GCs in photopic conditions than responsive GCs in scotopic conditions. (3) Gap junctions slow down GCs’ scotopic light responses and increase GCs’ ratio of antagonistic to center inputs. (4) Cone pathways do not affect the kinetics but alter the ratio of antagonistic to center inputs of scotopic GC responses, and they speed up GCs photopic responses and alter the ratio of GCs’ antagonistic to center synaptic inputs and receptive field profiles. (5) Rod bipolar cells shorten response latency of ON GCs and increase the ratio of GCs’ antagonistic to center synaptic inputs. (6) Light adaptation speeds up GCs’ temporal processing and tunes GC photopic responses to higher frequencies, and the tertiary rod pathway plays a significant role in adaptation-induced TTP changes in some GCs. (7) GC RF center sizes are partially mediated by AIIACs and GC-GC coupling. (8) Connexin36 gap junctions and cone pathways alter synaptic circuits underlying antagonistic surround inputs to GCs in photopic conditions.

Purpose Functional adaptation to ambient light is a key characteristic of retinal ganglion cells (RGCs), but little is known about how adaptation is affected by factors that are harmful to RGC health. We explored adaptation-induced changes to RGC physiology when exposed to increased intraocular pressure (IOP), a major risk factor for glaucoma. Methods Wild-type mice of both sexes were subjected to 2 weeks of IOP elevation using the bead model. Retinas were assessed using a multielectrode array to record RGC responses to checkerboard white noise stimulation under both scotopic and photopic light levels. This information was used to calculate a spike-triggered average (STA) for each RGC with which to compare between lighting levels. Results Low but not high IOP elevation resulted in several distinct RGC functional changes: (1) diminished adaptation-dependent receptive field (RF) center-surround interactions; (2) increased likelihood of a scotopic STA; and (3) increased spontaneous firing rate. Center RF size change with lighting level varied among RGCs, and both the center and surround STA peak times were consistently increased under scotopic illumination, although none of these properties were impacted by IOP level. Conclusions These findings provide novel evidence that RGCs exhibit reduced light-dependent adaptation and increased excitability when IOP is elevated to low but not high levels. These results may reveal functional changes that occur early in glaucoma, which can potentially be used to identify patients with glaucoma at earlier stages when intervention is most beneficial.

Elevation of intraocular pressure (IOP) causes retinal ganglion cell (RGC) dysfunction and death and is a major risk factor for glaucoma. We used a bead injection technique to increase IOP in mice of both genders by an average of ∼3 mmHg for 2 weeks. This level of IOP elevation was lower than that achieved in other studies, which allowed for the study of subtle IOP effects. We used multielectrode array recordings to determine the cellular responses of RGCs exposed to this mild degree of IOP elevation. We found that RGC photopic receptive field (RF) center size and whole-field RGC firing rates were unaffected by IOP elevation. In contrast, we found that the temporal properties of RGC photopic responses in the RF center were accelerated, particularly in ON sustained cells. We also detected a loss of antagonistic surround in several RGC subtypes. Finally, spontaneous firing rate, interspike interval variance, and contrast sensitivity were altered according to the magnitude of IOP exposure and also displayed an IOP-dependent effect. Together, these results suggest that individual RGC physiologic parameters have unique IOP-related functional thresholds that exist concurrently and change following IOP elevation according to specific patterns. Furthermore, even subtle IOP elevation can impart profound changes in RGC function, which in some cases may occur in an IOP-dependent manner. This system of overlapping functional thresholds likely underlies the complex effects of elevated IOP on the retina.SIGNIFICANCE STATEMENTRetinal ganglion cells (RGCs) are the obligate output neurons of the retina and are injured by elevated intraocular pressure (IOP) in diseases such as glaucoma. In this study, a subtle elevation of IOP in mice for 2 weeks revealed distinct IOP-related functional thresholds for specific RGC physiologic parameters and sometimes showed an IOP-dependent effect. These data suggest that overlapping IOP-related thresholds and response profiles exist simultaneously in RGCs and throughout the retina. These overlapping thresholds likely explain the range of RGC responses that occur following IOP elevation and highlight the wide capacity of neurons to respond in a diseased state.

Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease.

Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of these functional properties, such as receptive field size, are driven by specific retinal circuits. In this report, we determined the role of the ON bipolar cell mediated crossover circuitry in shaping the center and surround of OFF RGCs. We recorded from a large population of mouse RGCs using a multielectrode array while pharmacologically removing the ON-bipolar cell-mediated crossover circuit. OFF sustained and transient responses to whole field stimuli are lost under scotopic conditions, but maintained under photopic conditions. Though photopic light responses were grossly maintained, we found that photopic light response properties were altered. Using linear receptive field mapping, we found a significant reduction in the antagonistic surround and a decrease in size of the receptive field center. Using a novel approach to separate the distinct temporal filters present in the receptive field center, we see that the crossover pathway contributes specifically to the sluggish antagonistic filter in the center. These results provide new insight into the role of crossover pathways in driving RGCs and also demonstrate that the distinct inputs driving the receptive field center can be isolated and assayed by RGC activity.

The remarkable dynamic range of vision is facilitated by adaptation of retinal sensitivity to ambient lighting conditions. An important mechanism of sensitivity adaptation is control of the spatial and temporal window over which light is integrated. The retina accomplishes this by switching between parallel synaptic pathways with differing kinetics and degrees of synaptic convergence. However, the relative shifts in spatial and temporal integration are not well understood - particularly in the context of the antagonistic spatial surround. Here, we resolve these issues by characterizing the adaptation-induced changes to spatiotemporal integration in the linear receptive field center and surround of mouse retinal ganglion cells. While most ganglion cells lose their antagonistic spatial surround under scotopic conditions, a strong surround is maintained in a subset. We then applied a novel technique that allowed us to analyze the receptive field as a triphasic temporal filter in the center and a biphasic filter in the surround. The temporal tuning of the surround was relatively maintained across adaptation conditions compared to the center, which greatly increased its temporal integration. Though all phases of the center's triphasic temporal response slowed, some shifted significantly less. Additionally, adaptation differentially shifted ON and OFF pathway temporal tuning, reducing their asymmetry under scotopic conditions. Finally, spatial integration was significantly increased by dark adaptation in some cells while it decreased it in others. These findings provide novel insight into how adaptation adjusts visual information processing by altering fundamental properties of ganglion cell receptive fields, such as center-surround antagonism and space-time integration.

Multitasking negatively influences the retention of information over brief periods of time. This impact of interference on working memory is exacerbated with normal aging. We used functional MRI to investigate the neural basis by which an interruption is more disruptive to working memory performance in older individuals. Younger and older adults engaged in delayed recognition tasks both with and without interruption by a secondary task. Behavioral analysis revealed that working memory performance was more impaired by interruptions in older compared with younger adults. Functional connectivity analyses showed that when interrupted, older adults disengaged from a memory maintenance network and reallocated attentional resources toward the interrupting stimulus in a manner consistent with younger adults. However, unlike younger individuals, older adults failed to both disengage from the interruption and reestablish functional connections associated with the disrupted memory network. These results suggest that multitasking leads to more significant working memory disruption in older adults because of an interruption recovery failure, manifest as a deficient ability to dynamically switch between functional brain networks.

Reverse correlation methods such as spike‐triggered averaging consistently identify the spatial center in the linear receptive fields (RFs) of retinal ganglion cells (GCs). However, the spatial antagonistic surround observed in classical experiments has proven more elusive. Tests for the antagonistic surround have heretofore relied on models that make questionable simplifying assumptions such as space–time separability and radial homogeneity/symmetry. We circumvented these, along with other common assumptions, and observed a linear antagonistic surround in 754 of 805 mouse GCs. By characterizing the RF's space–time structure, we found the overall linear RF's inseparability could be accounted for both by tuning differences between the center and surround and differences within the surround. Finally, we applied this approach to characterize spatial asymmetry in the RF surround. These results shed new light on the spatiotemporal organization of GC linear RFs and highlight a major contributor to its inseparability.