Imaging Neural Circuits Underlying Learning and Behavior
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Sensory perception is context dependent and is likely modulated by task demands, learning and engagement to best serve specific goals of the organism. Sensory-driven behaviors also engage a cascade of cortical regions to process sensory input and generate motor output. To investigate the temporal dynamics of neural activity at this global scale, we have improved and integrated tools to perform functional imaging across large areas of cortex using a transgenic mouse expressing a fluorescent activity sensor. Imaging during an orientation discrimination task reveals a progression of activity in different cortical regions associated with different phases of the task. After cortex-wide patterns of activity are determined, we demonstrate the ability to select a region that displayed conspicuous responses for two-photon microscopy, and find that activity in populations of individual neurons in that region correlates with locomotion in trained mice. We also found that learning a visual discrimination reduced population activity in visual cortex. To further investigate this phenomenon, we used two-photon microscopy to image mice before or after they had learned a visual discrimination. We find that excitatory neurons in layer 2/3 show striking diversity in their temporal dynamics during the behavior and classify them into transient, sustained, and suppressed groups. Notably, these groups exhibit different visual tuning and modulation by locomotion. The functionally defined cell classes are also differentially modulated by training condition: showing both a cell class specific decrease in fraction responsive to visual stimuli after learning, and an increase in modulation by task engagement specific to trained animals. The characterization of pyramidal neuron subtypes in layer 2/3 of V1, and quantification of their distinct changes over learning, provides new insight into the circuit elements and pathways that enable goal-directed sensory processing. This dissertation includes published and unpublished co-authored material. This dissertation also includes four supplemental movies related to functional imaging techniques described in chapter II.