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      Anatomically segregated basal ganglia pathways allow parallel behavioral modulation

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          Abstract

          In the basal ganglia (BG), anatomically segregated and topographically-organized feedforward circuits are thought to modulate multiple behaviors in parallel. Although topographically-arranged BG circuits have been described, the extent to which these relationships are maintained across the BG output nuclei and in downstream targets is unclear. Here, using focal transsynaptic anterograde tracing, we show that the motor-action related topographical organization of the striatum is preserved in all BG output nuclei. The topography is also maintained downstream of the BG and in multiple parallel closed loops that provide striatal input. Furthermore, focal activation of two distinct striatal regions induce either licking or turning, consistent with the structure of projections to targets outside the BG. Our results confirm the parallel model of BG function, and suggest that the integration and competition of information relating to different behavior occurs largely outside of the BG.

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          Most cited references59

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          Parallel organization of functionally segregated circuits linking basal ganglia and cortex.

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            A mesoscale connectome of the mouse brain.

            Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.
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              Independent Optical Excitation of Distinct Neural Populations

              Optogenetic tools enable the causal examination of how specific cell types contribute to brain circuit functions. A long-standing question is whether it is possible to independently activate two distinct neural populations in mammalian brain tissue. Such a capability would enable the examination of how different synapses or pathways interact to support computation. Here we report two new channelrhodopsins, Chronos and Chrimson, obtained through the de novo sequencing and physiological characterization of opsins from over 100 species of algae. Chrimson is 45 nm red-shifted relative to any previous channelrhodopsin, important for scenarios where red light would be preferred; we show minimal visual system mediated behavioral artifact in optogenetically stimulated Drosophila. Chronos has faster kinetics than any previous channelrhodopsin, yet is effectively more light-sensitive. Together, these two reagents enable crosstalk-free two-color activation of neural spiking and downstream synaptic transmission in independent neural populations in mouse brain slice.
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                Author and article information

                Journal
                9809671
                21092
                Nat Neurosci
                Nat Neurosci
                Nature neuroscience
                1097-6256
                1546-1726
                7 September 2020
                28 September 2020
                November 2020
                28 March 2021
                : 23
                : 11
                : 1388-1398
                Affiliations
                [1 ]Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
                [2 ]Lead Contact
                Author notes

                Author Contributions

                Conceptualization, J.L. and B.L.S.; Investigation, J.L., W.W. Writing – Original Draft, J.L. and B.L.S.; Writing – Review & Editing, J.L. and B.L.S.; Supervision, B.L.S.; Funding Acquisition, B.L.S.

                Article
                NIHMS1622624
                10.1038/s41593-020-00712-5
                7606600
                32989293
                522b7ece-18a3-453c-94f7-e99a515cdabc

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                Article

                Neurosciences
                basal ganglia,striatum,substantia nigra reticulata,anterograde tracing,topography
                Neurosciences
                basal ganglia, striatum, substantia nigra reticulata, anterograde tracing, topography

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