Input-independent homeostasis of developing cortical attention states
Open AccessThis dissertation is part of current research at the Laboratory of Systems Neural Development at George Washington University for investigating the development of Visual Cortex (VC). This research contributed to understanding the underlying mechanisms that partake in cortical attention states’ developmental onset, which is the foundation for our insight into attention deficit disorders. These disorders result from disruptions in a normal cortical developmental process (P. Fries et al., 2001; Harris & Thiele, 2011; Harwerth et al., 1983). This research tested the hypothesis that cortical attention states are dependent on early sensory experience. The visual cortex of adult and young C57BL6 wild-type mice was selected as a model because of the ease in manipulating early sensory experience. We asked two questions: does removal of the sense organ change the developmental trajectory of cortical attention-like states? And does sensory deprivation affect the development of these states in adults? For the first experiment, littermates were enucleated at postnatal day 6 (enP6) or 13 (enP13), and the development of cortical activities associated with attention was monitored until P17, when they are primarily matured. For the adult experiments, enucleated at enP6, enP13, or received binocular lid-suture at P12 (ES) which prevents normal sensory experience but leaves the retina intact. For all experiments, littermate controls received Sham surgery. The experiments were performed via extracellular multi-electrode array recordings of primary visual cortex on head-fixed, unanesthetized mice. The collected signals are classified into local field potentials (LFPs) and multi-unit activity (MUAs) via band-pass filters. The LFPs’ power and spectral analysis are studied for both young and adult animals. Additionally, MUAs are analyzed to demonstrate the level of network activity during the development. The results in young mice, reported in Chapter 4, showed they largely preserve the developmental trajectory of cortical oscillations and firing rates despite the removal of their primary input. We did observe a period around eye-opening when the activity of enucleated animals was less continuous than controls in the enP6. However, this effect disappeared by P16 and was not observed in the enP13 group. Together these results suggest that a robust homeostatic process in the cortex regulated cortical activity development. In adult mice (Chapter 5), we found that neither enucleation nor visual deprivation strongly affected the expression of cortical attention states. Eye-sutured mice showed a slight reduction in neuron firing rates (2-4 Hz) while facing patterned stimulus. Additionally, Enucleated mice showed a reduced low-frequency activity during active attention state (within 5-12 Hz). In total, our results suggest that the normal acquisition of adult cortical states is independent of normal vision and only mildly regulated by the presence of the eye. This study shows that the regulation of cortical attention states is a process largely independent of the sensory experience.
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