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      Dendritic mGluR2 and perisomatic Kv3 signaling regulate dendritic computation of mouse starburst amacrine cells

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          Abstract

          Dendritic mechanisms driving input-output transformation in starburst amacrine cells (SACs) are not fully understood. Here, we combine two-photon subcellular voltage and calcium imaging and electrophysiological recording to determine the computational architecture of mouse SAC dendrites. We found that the perisomatic region integrates motion signals over the entire dendritic field, providing a low-pass-filtered global depolarization to dendrites. Dendrites integrate local synaptic inputs with this global signal in a direction-selective manner. Coincidental local synaptic inputs and the global motion signal in the outward motion direction generate local suprathreshold calcium transients. Moreover, metabotropic glutamate receptor 2 (mGluR2) signaling in SACs modulates the initiation of calcium transients in dendrites but not at the soma. In contrast, voltage-gated potassium channel 3 (Kv3) dampens fast voltage transients at the soma. Together, complementary mGluR2 and Kv3 signaling in different subcellular regions leads to dendritic compartmentalization and direction selectivity, highlighting the importance of these mechanisms in dendritic computation.

          Abstract

          How starburst amacrine cell (SAC) dendrites transform concentrically distributed synaptic inputs into branch-specific directional outputs is not fully understood. Here the authors report that dendritic mGluR2 signaling and somatic Kv3-mediated shunting coordinately implement SAC dendritic direction selectivity.

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          Most cited references54

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          Ultra-sensitive fluorescent proteins for imaging neuronal activity

          Summary Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultra-sensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies, and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5 - 40 micrometers long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.
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            Metabotropic glutamate receptors: physiology, pharmacology, and disease.

            The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
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              Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics.

              Patterns of gene expression can be used to characterize and classify neuronal types. It is challenging, however, to generate taxonomies that fulfill the essential criteria of being comprehensive, harmonizing with conventional classification schemes, and lacking superfluous subdivisions of genuine types. To address these challenges, we used massively parallel single-cell RNA profiling and optimized computational methods on a heterogeneous class of neurons, mouse retinal bipolar cells (BCs). From a population of ∼25,000 BCs, we derived a molecular classification that identified 15 types, including all types observed previously and two novel types, one of which has a non-canonical morphology and position. We validated the classification scheme and identified dozens of novel markers using methods that match molecular expression to cell morphology. This work provides a systematic methodology for achieving comprehensive molecular classification of neurons, identifies novel neuronal types, and uncovers transcriptional differences that distinguish types within a class.
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                Author and article information

                Contributors
                weiw@uchicago.edu
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                28 February 2024
                28 February 2024
                2024
                : 15
                : 1819
                Affiliations
                [1 ]Graduate Program in Biophysical Sciences, The University of Chicago, ( https://ror.org/024mw5h28) Chicago, IL 60637 USA
                [2 ]The Committee on Neurobiology Graduate Program, The University of Chicago, ( https://ror.org/024mw5h28) Chicago, IL 60637 USA
                [3 ]The Committee on Computational Neuroscience Graduate Program, The University of Chicago, ( https://ror.org/024mw5h28) Chicago, IL 60637 USA
                [4 ]Department of Ophthalmology, Stanford University, ( https://ror.org/00f54p054) Stanford, CA 94305 USA
                [5 ]Department of Neurobiology, Department of Bioengineering, Stanford University, ( https://ror.org/00f54p054) Stanford, CA 94305 USA
                [6 ]Department of Neurobiology and the Neuroscience Institute, The University of Chicago, ( https://ror.org/024mw5h28) Chicago, IL 60637 USA
                [7 ]GRID grid.38142.3c, ISNI 000000041936754X, Present Address: F.M. Kirby Neurobiology Center, Boston Children’s Hospital, , Harvard Medical School, ; Boston, MA 02115 USA
                [8 ]GRID grid.38142.3c, ISNI 000000041936754X, Present Address: Department of Neurobiology, , Harvard Medical School, ; Boston, MA 02115 USA
                [9 ]Present Address: Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, ( https://ror.org/05t99sp05) Berkeley, CA 94720 USA
                [10 ]Present Address: Department of Physiology & Biophysics, University of Washington, ( https://ror.org/00cvxb145) Seattle, WA 98195 USA
                Author information
                http://orcid.org/0000-0003-2282-6615
                http://orcid.org/0009-0007-5143-8538
                http://orcid.org/0000-0001-7367-8347
                http://orcid.org/0000-0003-1563-9117
                http://orcid.org/0000-0002-0492-1961
                http://orcid.org/0000-0002-7771-5974
                Article
                46234
                10.1038/s41467-024-46234-7
                10901804
                38418467
                de801cf4-5ef7-4650-95c0-8d6c7e12cb52
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 December 2021
                : 20 February 2024
                Funding
                Funded by: FundRef https://doi.org/10.13039/100000065, U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS);
                Award ID: R01 NS109990
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/100005270, McKnight Foundation;
                Award ID: McKnight Scholar Award
                Award Recipient :
                Categories
                Article
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                © Springer Nature Limited 2024

                Uncategorized
                ion channels in the nervous system,retina,dendritic excitability,membrane potential,sensory processing

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