Synaptomic analysis of dopaminergic inputs reveal hub synapses in the mouse striatum
| Autor: | Etienne Herzog, Paul Lapios, Vincent Paget-Blanc, Sabrina Lacomme, Maria-Florencia Angelo, Véronique Desmedt-Peyrusse, Stéphane Claverol, Thomas Biederer, Roman Walle, David Perrais, Vincent Pitard, Melina Petrel, Marie Pronot, Fabrice P. Cordelières, Christelle Martin, Marlene E. Pfeffer, Florian Levet, Pierre Trifilieff |
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| Přispěvatelé: | Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Interdisciplinary Institute for Neuroscience (IINS), Plateforme Métabolome-Fluxome du Centre de Génomique Fonctionnelle de Bordeaux, Institut National de la Recherche Agronomique (INRA), Université de Bordeaux (UB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
[SDV]Life Sciences [q-bio] Dopaminergic [SDV.BC]Life Sciences [q-bio]/Cellular Biology Striatum Biology Inhibitory postsynaptic potential Spine apparatus Synapse 03 medical and health sciences Glutamatergic 0302 clinical medicine Dopamine medicine [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Active zone Neuroscience 030217 neurology & neurosurgery 030304 developmental biology medicine.drug |
| Popis: | SUMMARYDopamine is a monoamine involved in reward processing and motor control. Volume transmission is thought to be the mechanism by which monoamines modulate effector systems at glutamate and GABA synapses. Hence, dopamine synapses are scarcely described. We applied fluorescence activated synaptosome sorting to explore the features of the dopaminergic synaptome. We provide the proteome of striatal dopaminergic synapses with 57 proteins specifically enriched. Beyond canonical markers of dopamine neurotransmission (Th, Slc6a3/DAT, Slc18a2/VMAT2), we validated 6 proteins belonging to pre- and postsynaptic sides (Cpne7, Apba1/Mint1, Cadps2, Cadm2/SynCAM 2, Stx4 and Mgll). Moreover, dopaminergic varicosities adhere to both a post-synapse with cognate receptors and glutamatergic, GABAergic or cholinergic synapses in structures we named dopaminergic “hub synapses”. Markers of presynaptic vesicles and active zone, post-synaptic density and spine apparatus, are significantly increased upon association with dopamine inputs in hubs. Thus neuromodulation frequently operates from hub synapses affecting associated synapses and is not solely dependent on volume transmission. Finally, FASS provides a new framework for the exploration of dopaminergic synapses and more generally for discrete synapse populations ex-vivo.HighlightsA first proteome of dopaminergic synapses in the striatumStriatal dopaminergic synaptosomes display post-synaptic cognate receptorsDopaminergic projections build hub synapses with excitatory, inhibitory, and cholinergic projections.Cortico-striatal synaptic scaffolds are strengthened upon association in hub synapses. |
| Databáze: | OpenAIRE |
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