Almost 200 years ago, Jan Purkinje examined the visual illusions induced by flickering light. Since then, scientists, clinicians, and artists have been fascinated by the effects of flicker on brain rhythms. When entrained with rhythmic light of ~10, ~20, ~40 Hz, visual cortex responds more strongly, or resonates. In the visual and cognitive neurosciences, resonance flicker is used to study perception and attention; in clinical domain, aberrant resonance responses to flicker are used as a diagnostic tool and potential treatment. However, the neural mechanisms by which flicker engages resonant properties of local cortical circuits and entrains brain rhythms at the level they are generated remain unknown. Over the past decade, this level became accessible to neuroscientists due to the rapid development of new neurobiological tools such as cell-type-specific optical stimulation (optogenetics). In this project, using recordings that span multiple spatial scales (from neurons and local field potentials across cortical layers to EEG), I will characterize the neural mechanisms by which flicker stimuli engage resonant properties of brain rhythms. I will use optogenetic tools to identify and manipulate genetically targeted cell types, and will combine it with simultaneous EEG and high-density laminar recordings in primary visual cortex of awake mice. I will determine the laminar profile of neural activity underlying flicker resonance observed at the EEG level (Study 1). By recording from distinct GABAergic interneuron classes and optogenetically silencing them, I will test the novel hypothesis that distinct classes of interneurons mediate flicker resonance to low (theta, alpha) and high (beta, gamma) frequencies (Study 2). This research will allow me to uncover the neurophysiological basis of resonance responses to flicker in unprecedented detail, and provide means to exploit the untapped potential of flicker as a tool to study and modulate brain rhythms in a targeted way.
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