Fundamental to our perception of a unified and stable environment is the capacity to combine information across the senses. Although this process appears seamless as an adult, the brain’s ability to successfully perform multisensory cue combination takes years to develop and relies on a number of complex processes including cue integration, cue calibration, causal inference, and reference frame transformations. Further complexities exist because multisensory cue combination is implemented by populations of noisy neurons. In this review, we discuss recent behavioral studies exploring how the brain combines information from different sensory systems, neurophysiological studies relating behavior to neuronal activity, and a theory of neural sensory encoding that can account for many of these experimental findings.

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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 ϳ3 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.

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.

Retinal ganglion cells (RGCs) are often grouped based on their functional properties. Many of these functional properties, such as receptive field (RF) size, are driven by specific retinal circuits. In this report, we determined the role of the ON bipolar cell (BC) 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 (MEA) while pharmacologically removing the ON BC-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 RF mapping, we found a significant reduction in the antagonistic surround and a decrease in size of the RF center. Using a novel approach to separate the distinct temporal filters present in the RF 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 RF center can be isolated and assayed by RGC activity.