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Electrophysiological and Behavioral Testing Reveal Aberrant Visual Processing in Syngap1+/- Mice

thesis
posted on 25.04.2022, 23:03 by Charles Andrew MartinCharles Andrew Martin

  

Syngap1+/- is a mouse mode for intellectual disability and autism spectrum disorder where haploinsufficiency of the Syngap1 gene and therefore downregulation of SynGAP1 leads to early maturation of synapses within the brain within post-natal days fourteen and sixteen instead of at the normal developmental schedule of post-natal day thirty. This early-shifted timeline falls directly before the visual critical where binocular matching between inputs from the two eyes occurs, and during a period where neurons become selective to specific orientations. High-level visual and cognitive issues observed in autism spectrum disorder patients might follow from deficits in basic sensory processing development, but it is not yet understand how Syngap1 haploinsufficiency affects visual development and visual processing. Therefore, to characterize visual processing within the Syngap1+/- mouse model of autism spectrum disorder, acute electrophysiological recordings were performed within the monocular and binocular regions of the mouse visual cortex (V1). Responses to a series of visual stimuli were analyzed to measure and compare receptive field size, orientation selectivity, and binocularity between Syngap1+/- mice and littermate controls. In order to understand how potential deficits in physiology could translate into visual perception, a behavioral training protocol was implemented which isolated visual acuity in mice. In accordance with known developmental timelines in the visual cortex, it was found that the receptive field sizes of V1 neurons in Syngap1+/- mice were unchanged from wild type controls. However, these same neurons had wider tuning curves and lower firing rates than neurons in littermate controls. Ocular dominance was unaltered between Syngap1+/- and wild type mice, but this was possibly due to low sample sizes of neurons from the binocular regions of V1. At the behavioral level, lower visual acuities were discovered in Syngap1+/- mice with a size degree difference compared to littermate controls – a minor but significant difference. These results indicate a reduction in SynGAP1 expression has a perceivable effect on V1 development and function at both physiological and behavioral levels.

History

Degree Type

Master of Science in Biomedical Engineering

Department

Biomedical Engineering

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Maria Dadarlat Makin

Additional Committee Member 2

Tamara Kinzer-Ursem

Additional Committee Member 3

Estuardo Robles