Date on Master's Thesis/Doctoral Dissertation
8-2024
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Anatomical Sciences and Neurobiology
Degree Program
Anatomical Sciences and Neurobiology, PhD
Committee Chair
McGee, Aaron
Committee Member
Guido, William
Committee Member
Borghuis, Bart
Committee Member
Schneider, Eve
Author's Keywords
neuroscience; vision; development; plasticity; ocular-dominance; Ngr1
Abstract
Sensory systems throughout the brain require experience to aid in proper wiring during development. While forming, many sensory systems have periods of heightened sensitivity where alterations in the quality of experience can have a profound impact on cortical responses throughout life. These periods of heightened sensitivity have been coined critical periods. In the visual system of mice a critical period for ocular dominance has been well studied and defined between postnatal days nineteen and thirty-six. During this critical period, altering visual experience by suturing one eye closed called monocular deprivation (MD) shifts responses in cortex towards the non-deprived eye. Similar durations of MD after the visual system has developed do not have the same effect on cortical responses. Here, utilizing calcium imaging via 2-photon microscopy, we track the changes to individual neurons in primary visual cortex (V1). We find many changes to the functional properties of neurons in V1, but most significantly we uncover that reorganization of the functional properties of neurons during the critical period serves as the backbone for the adaptation to experience in V1. We find that during development many excitatory neurons in layer 2/3 (L2/3) of V1 are constantly changing their functional properties but preferentially reorganize to match alterations in experience via MD. We then probe two mechanisms governing the closure of the critical period to assess potential differences in functional properties of neurons controlled by these mechanisms. First, we explore the potential necessity of microglia in experience-dependent maturation of visual circuitry. Microglia are the resident immune cells in the brain. They constantly scavenge the extracellular space. Because of this, they have been implicated through indirect means to play a crucial role in sculpting neuronal circuitry. We eliminated microglia throughout the brain beginning at eye opening through the experience-dependent development of the visual system. Surprisingly, we found that the function of visual circuitry and experience-dependent plasticity in the visual system were unaltered in the absence of microglia. Second, we sought to illuminate potential differences in the change to functional properties of neurons in V1 in critical period plasticity and model of extended plasticity. Nogo receptor (ngr1) is a neuronal receptor and deletion of the ngr1 gene extends critical period-like plasticity for ocular dominance into adulthood. By tracking neurons in V1 and comparing the adaptation to experience in the functional properties of neurons in juvenile wild-type mice during the critical period, adult wild-type mice after the closure of the critical period, and adult ngr1 KO mice, we have determined how the magnitude and mechanisms replicate critical period ocular dominance plasticity in this model of extended sensitivity. All these studies shed light on the mechanisms of adaptation to experience and the difference in neuronal plasticity during development and after maturation.
Recommended Citation
Brown, Thomas Christopher, "Regulation and mechanisms of ocular dominance plasticity at cellular resolution." (2024). Electronic Theses and Dissertations. Paper 4433.
Retrieved from https://ir.library.louisville.edu/etd/4433
