Surinach, Daniel2021-06-292021-06-292020-08https://hdl.handle.net/11299/220573University of Minnesota M.S. thesis. August 2020. Major: Mechanical Engineering. Advisor: Suhasa Kodandaramaiah. 1 computer file (PDF); viii, 99 pages.The advent of genetically encoded calcium indicators, along with surgical preparations such as thinned skulls or refractive index matched skulls, have enabled mesoscale cortical activity imaging in head-fixed mice. Such imaging studies have revealed complex patterns of coordinated activity across the cortical surface during spontaneous behaviors, goal-directed behavior, locomotion, motor learning and perceptual decision making in head-fixed animals. However, neural activity during free, unrestrained behavior significantly differs from that recorded in head-fixed animals. Furthermore, freely moving animals exhibit a repertoire of behaviors that is vastly increased from head-fixed animals, and therefore the ability to perform mesoscale imaging of the cortex in freely behaving mice needs further investigation. Here we present the "Mesoscope", a miniature, head-mountable imaging device compatible with transparent polymer skulls recently developed by our group. With an 8x10 mm field of view, the Mesoscope can image most of the mouse dorsal cortex with a resolution ranging from 39.37 to 55.68 micrometers. The Mesoscope weighs 3.8 g (<15% of a mouse's body weight) and incorporates a magnetic interlocking mechanism that allows quick fixation (<1 s of temporary restraint) to a 3D-printed morphologically realistic transparent polymer skull (See-Shell) implanted on an awake mouse. Open-field behavior tests indicate neither the See-Shell implantation nor the addition of Mesoscope significantly inhibits locomotion. The Mesoscope employs an array of blue LEDs to illuminate the cortical surface uniformly, with up to 31 mW of light power. An additional green LED provides illumination for reflectance imaging of intrinsic optical signals arising from changes in cortical blood volume and oxygenation following neural activity. The LEDs are powered using a custom-designed printed circuit board that allows for fast LED switching on a microsecond scale. We have used the Mesoscope to record neural activity across the dorsal cortex in mice during in a variety of different behaviors described as follows: spontaneous neural activity under light isoflurane anesthesia, sensory evoked neural responses under light isoflurane anesthesia, spontaneous neural activity during free awake behavior, spontaneous neural activity during awake social behavior, and spontaneous neural activity during sleep. The Mesoscope employs compact optical and electrical technologies that can perform mesoscale imaging across the dorsal cortex in freely moving and behaving mice and will potentially open new avenues of scientific inquiry.enCalcium ImagingMesoscaleSocial BehaviorThesis or Dissertation