Development of semi-automatic data analysis algorithms to examine the influence of sensory stimuli on locomotion and striatal neural activities in rodent models
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Our brains are constantly integrating sensory and movement information as we navigate within our environment. Through millennium of evolution, human has learned to associate sensory information as cues to form motor plans. One example is that for almost all cultures, dance and music are tightly linked together an integrated form of performance and entertainment. However, it is yet unclear how our brain processes sensory information to coordinate a specific movement plan. In this Master Thesis, I investigated the brain region striatum that is known to play crucial roles in movement coordination and habit formation. To examine the effect of sensory inputs on locomotor behavior and striatal neural activities, we performed calcium imaging from the striatum of head fixed mice during voluntary locomotion. We injected AAV-syn-GCaMP7f virus into the striatum region to express the genetically encoded calcium sensor GCaMP7 in striatal neurons, and used a custom fluorescent microscope to measure intracellular calcium change from hundreds of labelled cells simultaneously. To examine how audio-visual stimulation impact movement behavior, we tracked mice’s speed using a spherical treadmill while applying sustained period of audio-visual stimulation at either 10 Hz or 145 Hz. To quantify the influence of audio-visual stimulation on different locomotion features, I developed several semi-automated algorithms in MATLAB to classify locomotion features, such as stationary periods, motion events, acceleration periods, deceleration period, and motion transitions. Furthermore, I optimized calcium imaging data processing pipelines and correlated striatal neural activity to various locomotion features. We found that audiovisual stimulation at both 10Hz and 145Hz increased locomotion, characterized as an increase in the percentage of time mice spent in motion events and a corresponding decrease in stationary period. However, only the145Hz stimulation, but not 10Hz stimulation promoted motion onset/offset transitions, and increased acceleration/deceleration probability. These results demonstrate that audiovisual stimulation can modulate locomotor activities in rodent models, and different patterns of audiovisual stimulation can selectively modulate different movement parameters. We also found that audiovisual stimulation increased the firing frequency of most responsive neurons regardless of mice’s movement state, suggesting that sensory information can further increase the excitability of some motion related striatal neurons both when the mice are moving and staying still. These results provide direct evidence that noninvasive audiovisual stimulation can modulate striatal neural activity, suggesting a basis for developing future noninvasive sensory stimulation based exercise and dance therapies for motor disorders that involve the striatum, such as Parkinson's disease. Future analysis of how audiovisual stimulation selectively modulates individual striatal neuron and striatal network during different aspects of movement will provide a more in-depth understanding of how sensory stimulation promote movement.