Understanding Learning and Memory: the Role of Theta Oscillations across the Brain

Learning and memory are complex cognitive processes that help the brain understand and respond to the world around us. They are dynamic and constantly adapting as new sensory information is perceived and interpreted to make an appropriate response. However, the precise mechanisms underlying these processes, and how they are disrupted in learning disabilities, remain unknown. Recently, theta oscillations have been identified as a potential hallmark of visual familiarity encoding, as they emerge following passive exposure to a stimulus and are impaired in Fragile X syndrome (FX), a genetic form of autism spectrum disorder. Using acute in-vivo electrophysiological recordings with the Neuropixels probe, active learning paradigms, and multiple mouse strains, this dissertation further investigates the relationship between theta oscillations and these processes. First, we found that theta oscillations in the primary visual cortex and hippocampus emerge independently following passive familiarity, with temporal delays observed in a downstream region, the retrosplenial cortex. Second, FX mice exhibited impaired learning in a Go/No-Go visual discrimination task, which correlated with diminished theta oscillations. Third, increased theta power in wild-type mice was significantly associated with correct behavioral responses. Finally, we demonstrated that controlled neural plasticity is essential for theta oscillations to emerge following familiarity, as they are absent in histone deacetylase 4, 5 double knockout mice which lack this control. Overall, this work further links theta oscillations to the processes of learning and memory, providing new insights into the underlying mechanisms of these complex cognitive functions.