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West, S. L.

Publications and source records attributed to West, S. L..

3 recordsLinked to original sources

Wide-field calcium imaging of cortical activation and functional connectivity in externally- and internally-driven locomotion

The neural dynamics underlying self-initiated versus sensory driven movements is central to understanding volitional action. Upstream motor cortices are associated with the generation of internally-driven movements over externally-driven. Here we directly compare cortical dynamics during internally- versus externally-driven locomotion using wide-field Ca2+ imaging. We find that secondary motor cortex (M2) plays a larger role in internally-driven spontaneous locomotion transitions, with increased M2 functional connectivity during starting and stopping than in the externally-driven, motorized treadmill locomotion. This is not the case in steady-state walk. In addition, motorized treadmill and spontaneous locomotion are characterized by markedly different patterns of cortical activation and functional connectivity at the different behavior periods. Furthermore, the patterns of fluorescence activation and connectivity are uncorrelated. These experiments reveal widespread and striking differences in the cortical control of internally- and externally-driven locomotion, with M2 playing a major role in the preparation and execution of the self-initiated 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↗

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↗