Michael Fitzpatrick

MSTP in PhD Training

Program: Neurosciences

Current advisor: Daniel Kerschensteiner, MD

Undergraduate university: Grinnell College, 2016

Enrollment year: 2016

Research summary
Homeostatic Plasticity in Retinal Illuminance-Detection Circuits Preserves Non-Image-Forming Visual Behaviors

Stable encoding of environmental variables is essential for organismal health and survival. At the level of individual neurons and neural circuits, homeostatic plasticity acts to maintain activity levels and achieve functional stability. However, it is unclear how and to what extent homeostatic plasticity can maintain behavioral activity at the level of the entire organism. We demonstrate that homeostatic plasticity can compensate for one such critical variable – environmental illuminance. Illuminance is detected and encoded within the retina by the M1 subclass of intrinsically photosensitive retinal ganglion cells (M1 ipRGCs), which integrate extrinsic signals from photoreceptors with their own intrinsic light responses to drive non-image-forming behaviors such as the pupillary light reflex (PLR) and circadian photoentrainment. Here, we expand upon structural evidence to show that type 6 bipolar (B6) cells functionally provide extrinsic photoreceptor-derived input to M1 ipRGCs. We used mice in which B6 cells were selectively removed during development (B6-DTA) and revealed that PLR magnitude, sensitivity, and kinetics were unchanged. Using a novel stimulus paradigm to better isolate the extrinsic photoreceptor-derived component of the PLR, we found only subtle changes in pupil responses for B6-DTA mice. Furthermore, B6-DTA mice were able to successfully photoentrain their circadian rhythms across a broad range of light levels. Our results show that homeostatic plasticity mechanisms in retinal illuminance-detection circuits can successfully preserve multiple behavioral responses. The mechanisms by which this plasticity is accomplished could reveal fresh insights into both the biology of retinal illuminance-detection circuits as well as novel strategies to preserve visual behaviors after injury.

Graduate publications
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.