Altered trajectory of visual circuit maturation in the superior colliculus of fragile X mice

Abstract

Purpose : Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and autism. FXS patients experience dysfunction in sensory processing in multiple domains, including somatosensation, audition, and vision. Previously, we demonstrated specific disruptions in visual circuit organization and function in the superior colliculus (SC) of adult FXS mice (Fmr1^-/y), providing a tractable model to elucidate the mechanisms underlying sensory dysfunction. Here we sought to understand when these deficits arise during the maturation of visual circuit function in the SC.

Methods : We used in vivo extracellular electrophysiology to determine the functional properties of visually-responsive neurons in the SC of juvenile Fmr1^-/y mice and wild type (WT) littermate controls ranging in age from postnatal day 15 (P15) to >P60 (N > 10 units and > 3 animals per group). Spiking responses of individual units to flashing spots (7.5 x 7.5 deg) on a gray background were used to determine receptive field (RF) size, shape, and ON/OFF substructure. Responses to drifting square waves (12 directions, 6 spatial frequencies [SF]) were used to determine orientation- and direction-selectivity (gOSI, gDSI), SF tuning, and linearity (F₁/F₀ ratio).

Results : For both WT and Fmr1^-/y mice we observed dynamic visual responses in the SC over the course of development to both types of stimuli shown. We found significant effects of age on evoked firing rate (P = 0.0214) and RF area (P = 0.0246), each increasing over development. Consistent with previous results, we found a significant effect of genotype on RF area (P = 0.0418), which was evident as early as P18-P22. Intriguingly, we found that the complement of RF types was distinct in Fmr1^-/y mice from P15-22 and after P60. We also found significant effects of age on gOSI (P < 0.0001) and gDSI (P < 0.0001), as well as tuning width (P < 0.0001) and F₁/F₀ ratio (P = 0.0011) of orientation-selective (OS) neurons. We also observed effects of genotype on evoked firing rate of OS neurons (P = 0.0044), which emerged between P23-27, and an interaction between genotype and age on gDSI (P = 0.0381).

Conclusions : These data suggest that visual tuning properties in the mouse SC undergo a prolonged period of maturation, the trajectory of which is altered in Fmr1^-/y mice.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.