Abstract
.Significance: Cellular layering is a hallmark of the mammalian neocortex with layer and cell type-specific connections within the cortical mantle and subcortical connections. A key challenge in studying circuit function within the neocortex is to understand the spatial and temporal patterns of information flow between different columns and layers.Aim: We aimed to investigate the three-dimensional (3D) layer- and area-specific interactions in mouse cortex in vivo.Approach: We applied a new promising neuroimaging method—fluorescence laminar optical tomography in combination with voltage-sensitive dye imaging (VSDi). VSDi is a powerful technique for interrogating membrane potential dynamics in assemblies of cortical neurons, but it is traditionally used for two-dimensional (2D) imaging. Our mesoscopic technique allows visualization of neuronal activity in a 3D manner with high temporal resolution.Results: We first demonstrated the depth-resolved capability of 3D mesoscopic imaging technology in Thy1-ChR2-YFP transgenic mice. Next, we recorded the long-range functional projections between sensory cortex (S1) and motor cortex (M1) in mice, in vivo, following single whisker deflection.Conclusions: The results show that mesoscopic imaging technique has the potential to investigate the layer-specific neural connectivity in the mouse cortex in vivo. Combination of mesoscopic imaging technique with optogenetic control strategy is a promising platform for determining depth-resolved interactions between cortical circuit elements.
Highlights
The mammalian neocortex plays an important role in higher brain function, including sensory perception, cognition, associative learning, and goal-directed motor control.[1]
Cortical surface, the neocortex is organized in such a way that it is both highly specialized, with defined areas dedicated to specific functions and/or sensory modalities, and highly integrative, with each area receiving converging inputs from different thalamic nuclei, other cortical areas, and several neuromodulatory systems.[1,2]
We further imaged the layer-specific functional projections between sensory cortex (S1) and motor cortex (M1) in mice in vivo following single whisker stimulation. The results prove this mesoscopic imaging technique has the potential to serve as a useful tool in investigating the layer-specific neural connectivity in the mouse cortex in vivo
Summary
The mammalian neocortex plays an important role in higher brain function, including sensory perception, cognition, associative learning, and goal-directed motor control.[1]. Cortical surface, the neocortex is organized in such a way that it is both highly specialized, with defined areas dedicated to specific functions and/or sensory modalities, and highly integrative, with each area receiving converging inputs from different thalamic nuclei, other cortical areas, and several neuromodulatory systems.[1,2] Another form of cortical organization is clearly evident orthogonal to these tangentially distributed maps.[2] The neocortex is classically divided along its depth into six anatomically defined layers, from superficial layer 1 to deep layer 6. Each layer contains distinct classes of cells that project cortically or subcortically, along with GABAergic interneuron types.[2,3] These local neocortical microcircuits (six layers of interconnected excitatory and inhibitory neurons) will process and integrate all the area-specific inputs from different thalamic nuclei, other cortical areas, and several neuromodulatory systems
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