Experience-Induced Interocular Plasticity of Vision in Infancy

Animal model studies of amblyopia have generally concluded that enduring effects of monocular deprivation (MD) on visual behavior (i.e., loss of visual acuity) are limited to the deprived eye, and are restricted to juvenile life. We have previously reported, however, that lasting effects of MD on visual function can be elicited in adulthood by stimulating visuomotor experience through the non-deprived eye. To test whether stimulating experience would also induce interocular plasticity of vision in infancy, we assessed in rats from eye-opening on postnatal day (P) 15, the effect of pairing MD with the daily experience of measuring thresholds for optokinetic tracking (OKT). MD with visuomotor experience from P15 to P25 led to a ~60% enhancement of the spatial frequency threshold for OKT through the non-deprived eye during the deprivation, which was followed by loss-of-function (~60% below normal) through both eyes when the deprived eye was opened. Reduced thresholds were maintained into adulthood with binocular OKT experience from P25 to P30. The ability to generate the plasticity and maintain lost function was dependent on visual cortex. Strictly limiting the period of deprivation to infancy by opening the deprived eye at P19 resulted in a comparable loss-of-function. Animals with reduced OKT responses also had significantly reduced visual acuity, measured independently in a discrimination task. Thus, experience-dependent cortical plasticity that can lead to amblyopia is present earlier in life than previously recognized

Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities.

In mammals, synchronization of the circadian pacemaker in the hypothalamus is achieved through direct input from the eyes conveyed by intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian photoentrainment can be maintained by rod and cone photoreceptors, but their functional contributions and their retinal circuits that impinge on ipRGCs are not well understood. Using mice that lack functional rods or in which rods are the only functional photoreceptors, we found that rods were solely responsible for photoentrainment at scotopic light intensities. Rods were also capable of driving circadian photoentrainment at photopic intensities at which they were incapable of supporting a visually guided behavior. Using mice in which cone photoreceptors were ablated, we found that rods signal through cones at high light intensities, but not at low light intensities. Thus, rods use two distinct retinal circuits to drive ipRGC function to support circadian photoentrainment across a wide range of light intensities

A Novel Mechanism for Switching a Neural System from One State to Another

An animal's ability to rapidly adjust to new conditions is essential to its survival. The nervous system, then, must be built with the flexibility to adjust, or shift, its processing capabilities on the fly. To understand how this flexibility comes about, we tracked a well-known behavioral shift, a visual integration shift, down to its underlying circuitry, and found that it is produced by a novel mechanism – a change in gap junction coupling that can turn a cell class on and off. The results showed that the turning on and off of a cell class shifted the circuit's behavior from one state to another, and, likewise, the animal's behavior. The widespread presence of similar gap junction-coupled networks in the brain suggests that this mechanism may underlie other behavioral shifts as well

Ganglion Cell Adaptability: Does the Coupling of Horizontal Cells Play a Role?

Background: The visual system can adjust itself to different visual environments. One of the most well known examples of this is the shift in spatial tuning that occurs in retinal ganglion cells with the change from night to day vision. This shift is thought to be produced by a change in the ganglion cell receptive field surround, mediated by a decrease in the coupling of horizontal cells. Methodology/Principal Findings: To test this hypothesis, we used a transgenic mouse line, a connexin57-deficient line, in which horizontal cell coupling was abolished. Measurements, both at the ganglion cell level and the level of behavioral performance, showed no differences between wild-type retinas and retinas with decoupled horizontal cells from connexin57-deficient mice. Conclusion/Significance: This analysis showed that the coupling and uncoupling of horizontal cells does not play a dominant role in spatial tuning and its adjustability to night and day light conditions. Instead, our data suggest that anothe

Longitudinal Quantification of Eye-Movement Impairments after Pontine Hemorrhage

IntroductionWe report a case of hypertrophic olivary degeneration due to pontine hemorrhage. A 59-year-old male with untreated hypertension suffered a primary pontine hemorrhage, which caused horizontal eye-movement limitation. Progressive neurological deterioration with involuntary eye and palatal movements began months after hemorrhage. This was accompanied by magnetic resonance imaging evidence of hypertrophic olivary degeneration at 4.5 months.BackgroundPrimary pontine hemorrhage often leads to impairment of eye movements and diplopia. Hypertrophic olivary degeneration can also emerge months after hemorrhage, producing involuntary pendular eye movements. Neither the natural history of voluntary eye movements nor the emergence of involuntary eye movements after pontine hemorrhage has been previously quantified.MethodsWe used an optokinetic task that enabled measurement of eye movements. It provided real-time feedback on the ability to track continuously and saccade quickly in a pursuit task. The feedback motivated the patient to use the system repeatedly in his home. From 3 months after hemorrhage, the patient used the system for 9 months, allowing us to quantify changes in his eye movements.ResultsHorizontal gaze impairments were manifest in our task as limitation in horizontal range of motion, as well as delay in initiation of the right eye’s movement during left-to-right pursuit. Improvement in these impairments was measured over the course of months 3–7 post hemorrhage. In addition, the emergence of vertical pendular nystagmus was identified in the subject at 4 months. Analysis of the eye-movement records revealed presymptomatic oscillatory eye movements whose amplitude had grown steadily over the course of 3 weeks, prior to a sharp increase in amplitude that coincided with the patient’s first report of oscillopsia. Horizontal pendular nystagmus emerged 7.4 months after the hemorrhage, primarily in the left eye.ConclusionAn eye-tracking system deployed in a patient’s home enabled prospective longitudinal quantification of the natural history and improvement in voluntary eye-movement impairments after pontine hemorrhage. It also characterized prospectively for the first time, the emergence of involuntary eye movements resulting from the rare complication of hypertrophic olivary degeneration. Results suggest that brief weekly measurements with an eye-tracker may allow early detection of this complication

audiomath: a Neuroscientist's Sound Toolkit

In neuroscientific experiments and applications, working with auditory stimuli demands software tools for generation and acquisition of raw audio, for composition and tailoring of that material into finished stimuli, for precisely timed presentation of the stimuli, and for experimental session recording. Numerous programming tools exist to approach these tasks, but their differing specializations and conventions demand extra time and effort for integration. In particular, verifying stimulus timing requires extensive engineering effort when developing new applications. This paper has two purposes. The first is to present audiomath (https://pypi.org/project/audiomath ), a sound software library for Python that prioritizes the needs of neuroscientists. It minimizes programming effort by providing a simple object-oriented interface that unifies functionality for audio generation, manipulation, visualization, decoding, encoding, recording, and playback. It also incorporates specialized tools for measuring and optimizing stimulus timing. The second purpose is to relay what we have learned, during development and application of the software, about the twin challenges of delivering stimuli precisely at a certain time, and of precisely measuring the time at which stimuli were delivered. We provide a primer on these problems and the possible approaches to them. We then report audio latency measurements across a range of hardware, operating systems and settings, to illustrate the ways in which hardware and software factors interact to affect stimulus presentation performance, and the resulting pitfalls for the programmer and experimenter. In particular, we highlight the potential conflict between demands for low latency, low variability in latency ("jitter"), cooperativeness, and robustness. We report the ways in which audiomath can help to map this territory and provide a simplified path toward each application's particular priority. By unifying audio-related functionality and providing specialized diagnostic tools, audiomath both simplifies and potentiates the development of neuroscientific applications in Python

2004) Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system

PURPOSE. To develop a simple, rapid method of quantifying the spatial vision of mice. METHODS. A rotating cylinder covered with a vertical sine wave grating was calculated and drawn in virtual three-dimensional (3-D) space on four computer monitors facing to form a square. C57BL/6 mice standing unrestrained on a platform in the center of the square tracked the grating with reflexive head and neck movements. The spatial frequency of the grating was clamped at the viewing position by repeatedly recentering the cylinder on the head. Acuity was quantified by increasing the spatial frequency of the grating until an optomotor response could not be elicited. Contrast sensitivity was measured at spatial frequencies between 0.03 and 0.35 cyc/deg. RESULTS. Grating acuity was measurable on the day of eye opening (postnatal day [P]15: mean acuity, 0.031 cyc/deg) and reached a maximum (ϳ0.4 cyc/deg) by P24. A peak in the contrast sensitivity function emerged on P16 (4.7, or 21% contrast at 0.064 cyc/deg). The peak remained at 0.064 cyc/ deg and climbed to a maximum sensitivity of 24.5, or 4% contrast, by P29. Acuity was obtained in each mouse in Ͻ10 minutes, and a detailed contrast sensitivity curve was generated in approximately 30 minutes. CONCLUSIONS. The virtual optomotor system provides a simple and precise method for rapidly quantifying mouse vision. Behavioral measures of vision in mice are essential for interpreting the results of experiments designed to reveal the cellular and molecular mechanisms of vision and visual development and for evaluating potential treatments for visual diseases

Gradiate: a radial sweep approach to measuring detailed contrast sensitivity functions from eye movements

The contrast sensitivity function (CSF) is an informative measure of visual health, but the practical difficulty of measuring it has impeded detailed analyses of its relationship to different visual disorders. Furthermore, most existing tasks cannot be used in populations with cognitive impairment. We analyzed detailed CSFs measured with a non-verbal procedure called “Gradiate”, which efficiently infers visibility from eye movements and manipulates stimulus appearance in real time. Sixty observers of varying age (38 with refractive error) were presented with moving stimuli. Stimulus spatial frequency and contrast advanced along fifteen radial sweeps through CSF space in response to stimulus-congruent eye movements. A point on the CSF was recorded when tracking ceased. Gradiate CSFs were reliable and in high agreement with independent low contrast acuity thresholds. Overall CSF variation was largely captured by two orthogonal factors (“radius” and “slope”), or two orthogonal shape factors when size was normalized (“aspect ratio” and “curvature”). CSF radius was highly predictive of LogMAR acuity, as were aspect ratio and curvature together, but only radius was predictive of observer age. Our findings suggest that Gradiate holds promise for assessing spatial vision in both verbal and non-verbal populations and indicate that variation between detailed CSFs can reveal useful information about visual health