Michael Fitzpatrick
Program: Neurosciences
Current advisor: Daniel Kerschensteiner, MD
Undergraduate university: Grinnell College
Research summary
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. Through the pupillary light reflex (PLR), the retina can encode increments in environmental illuminance and subsequently drive pupil constriction to attenuate the amount of light that reaches the retina. We find that the pupil control circuitry performs a second input-output transformation; namely, 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. 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. We uncover the neural mechanisms by which the B6-M1 circuit computes illuminance and contrast, revealing both cell-type-specific contributions as well as a high capacity for homeostatic plasticity in response to developmental perturbations. Using computational modeling and behavioral assays, we demonstrate that pupil constriction improves image contrast substantially more so than image brightness. Consequently, we show that pupil constriction improves acuity in gaze stabilization and predation in mice, supporting the hypothesis that pupil constriction can maximize acuity to enhance visual performance.
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, 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.
Graduate publications
Fitzpatrick MJ, Krizan J, Hsiang JC, Shen N, Kerschensteiner D. 2024 A pupillary contrast response in mice and humans: Neural mechanisms and visual functions. Neuron, 112(14):2404-2422.e9.
Krizan J, Song X, Fitzpatrick MJ, Shen N, Soto F, Kerschensteiner D. 2024 Predation without direction selectivity. Proc Natl Acad Sci USA, 121(12):e2317218121.
Fitzpatrick MJ, Kerschensteiner D. 2023 Homeostatic plasticity in the retina. Prog Retin Eye Res, 94():101131.
McCracken S, Fitzpatrick MJ, Hall AL, Wang Z, Kerschensteiner D, Morgan JL, Williams PR. 2023 Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo. Cell Rep, 42(10):113165.
Johnson KP, Fitzpatrick MJ, Zhao L, Wang B, McCracken S, Williams PR, Kerschensteiner D. 2021 Cell-type-specific binocular vision guides predation in mice. Neuron, 109(9):1527-1539.e4.
Sobieski C, Fitzpatrick MJ, Mennerick SJ. 2017 Differential Presynaptic ATP Supply for Basal and High-Demand Transmission. J Neurosci, 37(7):1888-99.