Abstract

All information about the visual world must first pass through the pupil before it is further encoded by the retina and transmitted to the rest of the visual system. Thus, changes in pupil diameter represent the very first step in visual processing. Pupillary constriction exhibits three main effects on the image that passes through the optics of the eye: 1) it attenuates the amount of light that reaches the retina; 2) it improves the depth of focus of the image; and 3) it reduces blur and enhances spatial contrast (i.e., maximizes visual acuity) by focusing light through the relatively aberration-free center of the lens. Through the pupillary light reflex (PLR), the retina can encode increments in environmental illuminance and subsequently drive pupil constriction in a classic and well-understood reflexive arc. Similarly, coordinated motor programs during fixation on a near object drive lens accommodation, ocular vergence, and pupil constriction (i.e., the pupillary near response, PNR) to deepen the focal plane. However, no circuits have been described which control pupillary responses to environmental contrast in order to optimize visual acuity and the transmission of high-frequency spatial contrast. In our first study, we describe such a response. We discover that the pupil constricts robustly to luminance-neutral temporal contrast modulation (the pupillary contrast response, PCoR) in both mice and humans in order to enhance spatial contrast in the retinal image and increase visual acuity. We find that the PCoR is mediated by the same reflexive arc that drives the PLR and is driven by a cell-type-specific pathway consisting of rod photoreceptors via type 6 bipolar cells (B6) and M1 ganglion cells. Temporal contrast is transformed into sustained pupil constriction by the M1's conversion of excitatory input into spike output. We use computational modeling to show how the PCoR shapes the spatial frequency content of retinal images, and we demonstrate that pupil constriction impacts image contrast substantially more so than image brightness. Consequently, we show that pupil constriction elevates cortical responses to spatial details and improves acuity in gaze stabilization and predation in mice, supporting the hypothesis that pupil constriction can maximize acuity. Fascinatingly, the PCoR and PLR share the same cell-type-specific pathway transmitting multiplexed contrast and illuminance signals through the mouse retina. However, both signals seem to be transmitted differently. Given the prominent contributions of B6 to both pathways, for our second study we investigated the effect of eliminating B6 from either the developing or the adult retina. We find an impressive degree of plasticity in this highly specific circuit when B6 is removed from developing animals and detail how the window for plasticity closes into adulthood. This homeostatic plasticity preserves the PLR and non-image-forming visual responses (e.g., circadian photoentrainment) with few obvious deficits. However, the tuning of the PCoR is altered, suggesting that B6 determines the contrast response properties of the PCoR and that the homeostatic rewiring replacing B6 imparts distinct properties to the circuit. In vision, as in other sensory modalities, information about the environment rarely arrives passively; rather, organisms actively seek and shape the sensory input they receive through active sensing. Here, we uncover how the pupil actively transforms visual input through a novel pupillary control circuit, the PCoR. Taken together, our studies describe the neural mechanisms mediating this response while illustrating its role in enhancing visual acuity and highlighting its capacity for homeostatic plasticity. These findings provide critical insight into how the retinal circuitry itself can serve to optimize the visual input it receives, opening new doors to understanding retinal encoding and the forces that shape visual behaviors.

Committee Chair

Daniel Kerschensteiner

Committee Members

Erik Herzog; Martha Bagnall; Steven Mennerick; Timothy Holy

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

3-13-2026

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-7663-2635

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Available for download on Friday, March 10, 2028

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Neurosciences Commons

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