Cell class-specific long-range axonal projections of neurons in mouse whisker-related somatosensory cortices
Year: 2024
Type: article
Abstract: The extensive long-range axonal projections of diverse classes of neocortical excitatory neurons are thought to contribute importantly to the highly integrative brain-wide interactions underlying the processing of sensory, cognitive and motor signals. Here, we investigated the long-range axonal output of various classes of genetically-defined projection neurons with cell bodies located in the whisker-related somatosensory cortices of the mouse through brain-wide light-sheet imaging of fluorescently-labeled axons segmented by specifically-trained convolutional networks quantified within the Allen Mouse Brain Atlas Common Coordinate Framework. We injected Cre-dependent virus to express GFP or tdTomato in the posterior primary somatosensory barrel cortex and the posterior supplemental somatosensory cortex, which contain the representations of the large posterior mystacial whiskers. We investigated the six following transgenic mouse lines which preferentially express Cre in different glutamatergic neocortical cell classes: Rasgrf2-dCre for layer 2/3 intratelencephalic projection neurons, Scnn1a-Cre for layer 4 intratelencephalic projection neurons, Tlx3-Cre for layer 5 intratelencephalic projection neurons, Sim1-Cre for layer 5 pyramidal tract projection neurons, Rbp4-Cre for layer 5 projection neurons and Ntsr1-Cre for layer 6 corticothalamic neurons. We found long-range axonal projections in many diverse downstream brain areas with largely similar output from primary and secondary cortices, but with genetically-defined cell classes showing distinct innervation patterns, with Rbp4-Cre mice showing the broadest innervation targets, subsets of which were innervated in the other mouse lines. To test whether the revealed axonal projections might underpin functional circuits, we compared the spatial organization of the axonal innervation with functional connectivity maps obtained from optogenetic stimulation of sensory cortex and wide-field imaging of the activity propagation to frontal cortices. Both methods indicated that neurons located more laterally in somatosensory cortex topographically signaled to more anteriorly located regions in motor cortex. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling, and, together with further technological advances, this will help provide increasingly detailed connectivity information of the mouse brain, essential for understanding the complex neuronal circuitry underlying even simple goal-directed behaviors.
Source: eLife
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: National Science Foundation, Brain Science Foundation, Royal Society, European Commission, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Ichiro Kanehara Foundation for the Promotion of Medical Sciences and Medical Care, Research Foundation for Opto-Science and Technology, Japan Society for the Promotion of Science, H2020 Marie Skłodowska-Curie Actions
Awards: Behavioral demand-driven dynamic reorganisation of cortical networks revealed by simultaneous wide-field optical imaging and optogenetic stimulation mapping in task-performing mice, G2639446237, Experienced Researchers Incoming Fellowship Programme at the Ecole Polytechnique Fédérale de Lausanne, Behavioral demand-driven dynamic reorganisation of cortical networks revealed by simultaneous wide-field optical imaging and optogenetic stimulation mapping in task-performing mice, Neural circuits for goal-directed sensorimotor transformation, Experienced Researchers Incoming Fellowship Programme at the Ecole Polytechnique Fédérale de Lausanne, Synaptic mechanisms of reward-based learning
OpenAlex ID: W4403333747