Circuit Mechanisms of Synchrony: Developing a Two-Pronged Approach Featuring a Novel Behavioral Paradigm and Gamma Neurofeedback

Abstract

In 1929, the German psychiatrist Hans Berger described the first human electroencephalographic (EEG) pattern, a rhythm of 8 to 12 Hz. Though this initially triggered a surge of research, because early on oscillations were linked to loss of consciousness states, the field assumed there was little connection between oscillations and cognitive brain function. Recently, there has been increasing evidence that oscillations, particularly in the gamma band (30-80 Hz), are important to cognitive functions, particularly attention. Oscillations are hypothesized to boost neural representations in target areas and reduce signal-tonoise transmission. A prevailing hypothesis suggests that gamma coherence across the sensory pathway underlies attention by enhancing information flow through the brain. Despite the increasing link between oscillations and cognition, the underlying mechanisms of how coherence emerges remain unknown. This project had two main aims. The first aim was built on a behavioral paradigm where mice were taught to behaviorally attend to or ignore stimuli across two sensory modalities: auditory and vibrissae. This novel behavioral paradigm will be coupled with multi-electrode recordings to visualize how the power of gamma oscillations are modulated by attention. This will allow to directly test our hypothesis that attention infuses gamma along the sensory pathway. If true, we expect to observe higher gamma coherence between SI and 6 SII while mice are attending to the vibrissae modality than when mice are attending to the auditory modality. We will also optogenetically induce gamma coherence between SI and SII to determine if this causally improves attention and therefore performance. Since the first step in employing a new behavioral paradigm is devising a successful training strategy, preliminary results have been based on our work optimizing the training protocol. Through a series of experimental manipulations, we have successfully trained mice to selectively respond to auditory stimuli. In the second aim, mice will be trained to increase the power of their gamma oscillations to brighten a light-emitting diode (LED). This will serve as a powerful tool for investigating how gamma oscillations are created and propagated. In order to launch this study, we developed tools for performing realtime gamma power analysis and updating behavioral stimuli correspondingly. With in-house capabilities to build chronic recording drives, we have perfected a 16-stereotrode chronic implant that will allow us to investigate gamma propagation across 15 nodes.