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. However, neural activity during unrestrained behavior substantially differs from neural activity in head-fixed animals. For whole-cortex imaging in freely behaving mice, we here present the “mini-mScope,” a wide-field, miniaturized, and head-mounted fluorescence microscope compatible with transparent polymer skull preparations. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the mini-mScope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 μm. We have used the mini-mScope to record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, social interactions, and transitions from wakefulness to sleep.
Electrophysiology and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have high temporal resolution, while optical imaging allows recording of genetically‐defined populations at high spatial resolution. Combining these two modalities for simultaneous large‐scale, multimodal sensing of neural activity across multiple brain regions can be very powerful. Here, transparent, inkjet‐printed electrode arrays with outstanding optical and electrical properties are seamlessly integrated with morphologically conformant transparent polymer skulls. Implanted on transgenic mice expressing the Calcium (Ca2+) indicator GCaMP6f in excitatory neurons, these “eSee‐Shells” provide a robust opto‐electrophysiological interface for over 100 days. eSee‐Shells enable simultaneous mesoscale Ca2+ imaging and electrocorticography (ECoG) acquisition from multiple brain regions covering 45 mm2 of cortex under anesthesia and in awake animals. The clarity and transparency of eSee‐Shells allow recording single‐cell Ca2+ signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca2+ signals that depend on the behavioral state.
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 cortex during spontaneous behaviors, goal-directed behavior, locomotion, motor learning, and perceptual decision making. However, neural activity during unrestrained behavior significantly differs from neural activity in head-fixed animals. Whole-cortex imaging in freely behaving mice will enable the study of neural activity in a larger, more complex repertoire of behaviors not possible in head-fixed animals. Here we present the “Mesoscope,” a wide-field miniaturized, head-mounted fluorescence microscope compatible with transparent polymer skulls recently developed by our group. With a field of view of 8 mm x 10 mm and weighing less than 4 g, the Mesoscope can image most of the mouse dorsal cortex with resolution ranging from 39 to 56 µm. Stroboscopic illumination with blue and green LEDs allows for the measurement of both fluorescence changes due to calcium activity and reflectance signals to capture hemodynamic changes. We have used the Mesoscope to successfully record mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions. Finally, combining the mesoscale imaging with electrophysiology enabled us to measure dynamics in extracellular glutamate release in the cortex during the transition from wakefulness to natural sleep.
Electrophysiological and optical imaging provide complementary neural sensing capabilities – electrophysiological recordings have the highest temporal resolution, while optical imaging allows recording the activities of genetically defined populations at high spatial resolution. Combining these complementary, yet orthogonal modalities to perform simultaneous large-scale, multimodal sensing of neural activity across multiple brain regions would be very powerful. Here we show that transparent, inkjet-printed electrocorticography (ECoG) electrode arrays can be seamlessly integrated with morphologically conformant transparent polymer skulls for multimodal recordings across the cortex. These ‘eSee-Shells’ were implanted on transgenic mice expressing the Ca2+ indicator GCaMP6f in cortical excitatory cells and provided a robust opto-electrophysiological interface for over 100 days. eSee-Shells enable simultaneous mesoscale Ca2+ imaging and ECoG acquisition under anesthesia as well as in awake animals presented with sensory stimuli. eSee-Shells further show sufficient clarity and transparency to observe single-cell Ca2+ signals directly below the electrodes and interconnects. Simultaneous multimodal measurement of cortical dynamics reveals changes in both ECoG and Ca2+ signals that depend on the behavioral state.
The mini-mScope is a wide-field miniaturized, head-mounted fluorescence microscope for imaging in freely behaving mice. We demonstrate recording mesoscale calcium activity across the dorsal cortex during sensory-evoked stimuli, open field behaviors, and social interactions.
Morphometric studies have provided crucial insights into the skull anatomy of commonly used wildtype (WT) laboratory mice strains such as the C57BL/6. With the increasing use of transgenic (TG) animals in neuroscience research, it is important to determine whether the results from morphometric studies performed on WT strains can be extended to TG strains derived from these WT strains. We report a new computer vision-based analysis pipeline for surveying mouse skull morphology using microcomputed tomography (micro-CT) scans. We applied this pipeline to study and compare eight cohorts of adult mice from two strains, including both male and female mice at two age points. We found that the overall skull morphology was generally conserved between cohorts, with only 13% of landmark distance differences reaching statistical significance. In addition, we surveyed the dorsal skull bone thickness differences between cohorts. We observed significantly thicker dorsal, parietal, and/or interparietal bones in WT, male, or older mice for 53% of thickness comparisons. This knowledge of dorsal skull bone thickness has potential implications for surgical planning through skull imaging and has applications in automating cranial microsurgeries on mice.
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