bioRxiv Science⌕ Search

Biology subjects

Ghanbari, L.

Publications and source records attributed to Ghanbari, L..

5 recordsLinked to original sources

Polymer skulls with integrated transparent electrode arrays for cortex-wide opto-electrophysiological recordings

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.

neuroscience↗

Wide-Field Calcium Imaging of Dynamic Cortical Networks During Locomotion

Motor behavior results in widespread activation of the cerebral cortex. Therefore, fully understanding the cerebral cortexs role in motor behavior requires a mesoscopic level description of the engaged cortical regions and their functional interactions. Mesoscopic imaging of Ca2+ fluorescence through transparent polymer skulls implanted on transgenic Thy1-GCaMP6f mice reveals widespread activation of the cerebral cortex during locomotion, including not only in primary motor and somatosensory regions but also in secondary motor, retrosplenial, and visual cortices. Using the time series of Ca2+ fluorescence from 28 regions (nodes) we found to be consistent across mice, we examined the changes in functional connectivity from rest to locomotion. At the initiation of locomotion, the most anterior nodes of the secondary motor cortex increase in correlation with other nodes, while other nodes decrease in correlation. Eigenvector centrality confirms these changes in functional connectivity. Directed Granger causality analysis reveals an increase in causal influence of anterior regions of secondary motor cortex on other dorsal cortical regions at the onset of locomotion. These results highlight the global changes in correlation, centrality, and causality occurring throughout the cerebral cortex between rest and locomotion and suggest that the premotor areas play an important role in organizing these changes.

neuroscience↗

Miniaturized head-mounted device for whole cortex mesoscale imaging in freely behaving mice

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 {micro}m. 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.

neuroscience↗

Cortex-wide neural interfacing via transparent polymer skulls

Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating cognition, perception and sensorimotor behaviors. Enormous progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. To fill this need, we have engineered \"See-Shells\" - digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>200 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 {micro}m through the See-Shells. See-Shells implanted on transgenic mice expressing genetically encoded calcium (Ca2+) indicators allow tracking of neural activities from multiple, non-contiguous regions spread across millimeters of the cortex. Further, neural probes can access the brain through perforated See-Shells, either for perturbing or recording neural activity from localized brain regions simultaneously with whole cortex imaging. As See-Shells can be constructed using readily available desktop fabrication tools and modified to fit a range of skull geometries, they provide a powerful tool for investigating brain structure and function.

neuroscience↗

Principles of Computer Numerical Controlled Machining Applied to Cranial Microsurgery

Over the last decade, a plethora of tools have been developed for neuroscientists to interface with the brain. Implementing these tools requires precise removal of sections of the skull to access the brain. These delicate cranial microsurgical procedures need to be performed on sub-millimeter thick bone without damaging the underlying tissue and therefore, require significant training. Automating some of these procedures would not only enable more precise microsurgical operations, but also democratize use of advanced neurotechnologies. Here, we describe the Craniobot, a cranial microsurgery platform that combines automated skull surface profiling with a computer numerical controlled (CNC) milling machine to perform a variety of cranial microsurgical procedures in mice. The Craniobot utilizes a low force contact sensor to profile the skull surface and uses this information to perform micrometer-scale precise milling operations within minutes. We have used the Craniobot to drill pilot holes to anchor cranial implants, perform skull thinning, and open small to large craniotomies. The Craniobot is built using off-the-shelf components for under $1000 and is controlled using open-source CNC programming software.

bioengineering↗